Table of Contents
Leukemia Research and Treatment
Volume 2012 (2012), Article ID 179402, 14 pages
http://dx.doi.org/10.1155/2012/179402
Review Article

Important Genes in the Pathogenesis of 5q- Syndrome and Their Connection with Ribosomal Stress and the Innate Immune System Pathway

1Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic
2Center of Experimental Hematology, First Medical Faculty, Charles University, Institute of Pathological Physiology, 128 53 Prague 2, Czech Republic

Received 25 September 2011; Revised 6 November 2011; Accepted 14 November 2011

Academic Editor: Daniela Cilloni

Copyright © 2012 Ota Fuchs. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Haase, U. Germing, J. Schanz et al., “New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients,” Blood, vol. 110, no. 13, pp. 4385–4395, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. R. P. Hasserjian, M. M. Le Beau, A. F. List et al., WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues, International Agency for Research on Cancer Press, Lyon, France, 2007.
  3. H. Van Den Berghe, J. J. Cassiman, and G. David, “Distinct haematological disorder with deletion of long arm of No. 5 chromosome,” Nature, vol. 251, no. 5474, pp. 437–438, 1974. View at Google Scholar · View at Scopus
  4. H. Van Den Berghe, K. Vermaelen, and C. Mecucci, “The 5q- anomaly,” Cancer Genetics and Cytogenetics, vol. 17, no. 3, pp. 189–255, 1985. View at Publisher · View at Google Scholar · View at Scopus
  5. S. D. Nimer and D. W. Golde, “The 5q-abnormality,” Blood, vol. 70, no. 6, pp. 1705–1712, 1987. View at Google Scholar · View at Scopus
  6. P. Mathew, A. Tefferi, G. W. Dewald et al., “The 5q- syndrome: a single-institution study of 43 consecutive patients,” Blood, vol. 81, no. 4, pp. 1040–1045, 1993. View at Google Scholar · View at Scopus
  7. J. Boultwood, S. Lewis, and J. S. Wainscoat, “The 5q- syndrome,” Blood, vol. 84, no. 10, pp. 3253–3260, 1994. View at Google Scholar · View at Scopus
  8. H. Van Den Berghe and L. Michaux, “5q-, twenty-five years later: a synopsis,” Cancer Genetics and Cytogenetics, vol. 94, no. 1, pp. 1–7, 1997. View at Publisher · View at Google Scholar · View at Scopus
  9. A. A. N. Giagounidis, U. Germing, J. S. Wainscoat, J. Boultwood, and C. Aul, “The 5q-syndrome,” Hematology, vol. 9, no. 4, pp. 271–277, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Mohamedali and G. J. Mufti, “Van-den Berghe's 5q- syndrome in 2008,” British Journal of Haematology, vol. 144, no. 2, pp. 157–168, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. C. L. Willman, C. E. Sever, M. G. Pallavicini et al., “Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia,” Science, vol. 259, no. 5097, pp. 968–971, 1993. View at Google Scholar · View at Scopus
  12. J. Boultwood, C. Fidler, S. Lewis et al., “Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome,” Blood, vol. 82, no. 9, pp. 2611–2616, 1993. View at Google Scholar · View at Scopus
  13. M. M. Le Beau, R. Espinosa, W. L. Neuman et al., “Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 12, pp. 5484–5488, 1993. View at Google Scholar · View at Scopus
  14. J. Boultwood, C. Fidler, S. Lewis et al., “Molecular mapping of uncharacteristically small 5q deletions in two patients with the 5q- syndrome: delineation of the critical region on 5q and identification of a 5q- breakpoint,” Genomics, vol. 19, no. 3, pp. 425–432, 1994. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Boultwood, C. Fidler, A. J. Strickson et al., “Narrowing and genomic annotation of the commonly deleted region of the 5q- syndrome,” Blood, vol. 99, no. 12, pp. 4638–4641, 2002. View at Publisher · View at Google Scholar · View at Scopus
  16. R. J. Jaju, J. Boultwood, F. J. Oliveret et al., “Molecular cytogenc definition of the critical deleted region in the 5q- syndrome,” Genes Chromosomes Cancer, vol. 22, pp. 251–256, 1998. View at Google Scholar
  17. N. Zhao, A. Stoffel, P. W. Wang et al., “Molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases to 1-1.5 Mb and preparation of a PAC-based physical map,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 13, pp. 6948–6953, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. M. L. Heaney and D. W. Golde, “Myelodysplasia,” The New England Journal of Medicine, vol. 340, no. 21, pp. 1649–1660, 1999. View at Publisher · View at Google Scholar · View at Scopus
  19. L. Nilsson, I. Astrand-Grundstrom, I. Arvidsson et al., “Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level,” Blood, vol. 96, no. 6, pp. 2012–2021, 2000. View at Google Scholar · View at Scopus
  20. K. M. Eisenmann, K. J. Dykema, S. F. Matheson et al., “5q- myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics,” Oncogene, vol. 28, no. 39, pp. 3429–3441, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Boultwood, A. Pellagatti, H. Cattan et al., “Gene expression profiling of CD34+ cells in patients with the 5q- syndrome,” British Journal of Haematology, vol. 139, no. 4, pp. 578–589, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. A. G. Knudson, “Mutation and cancer: statistical study of retinoblastoma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 68, no. 4, pp. 820–823, 1971. View at Google Scholar · View at Scopus
  23. A. J. W. Paige, “Redefining tumour suppressor genes: exceptions to the two-hit hypothesis,” Cellular and Molecular Life Sciences, vol. 60, no. 10, pp. 2147–2163, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. B. L. Ebert, “Deletion 5q in myelodysplastic syndrome: a paradigm for the study of hemizygous deletions in cancer,” Leukemia, vol. 23, no. 7, pp. 1252–1256, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Narla and B. L. Ebert, “Ribosomopathies: human disorders of ribosome dysfunction,” Blood, vol. 115, no. 16, pp. 3196–3205, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Tormo, I. Marugán, and M. Calabuig, “Myelodysplastic syndromes: an update on molecular pathology,” Clinical and Translational Oncology, vol. 12, no. 10, pp. 652–661, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. M. S. Davids and D. P. Steensma, “The molecular pathogenesis of myelodysplastic syndromes,” Cancer Biology and Therapy, vol. 10, no. 4, pp. 309–319, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. A. H. Berger and P. P. Pandolfi, “Haplo-insufficiency: a driving force in cancer,” Journal of Pathology, vol. 223, no. 2, pp. 137–146, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Montaville, Y. Dai, C. Y. Cheung et al., “Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22,” Biochimica et Biophysica Acta, vol. 1763, no. 11, pp. 1335–1343, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Jia, C. Tong, B. Wang, L. Luo, and J. Jiang, “Hedgehog signalling activity of smoothened requires phosphorylation by protein kinase A and casein kinase I,” Nature, vol. 432, no. 7020, pp. 1045–1050, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Hämmerlein, J. Weiske, and O. Huber, “A second protein kinase CK1-mediated step negatively regulates Wnt signalling by disrupting the lymphocyte enhancer factor-1/β-catenin complex,” Cellular and Molecular Life Sciences, vol. 62, no. 5, pp. 606–618, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Lehmann, J. O'Kelly, S. Raynaud, S. E. Funk, E. H. Sage, and H. P. Koeffler, “Common deleted genes in the 5q-syndrome: thrombocytopenia and reduced erythroid colony formation in SPARC null mice,” Leukemia, vol. 21, no. 9, pp. 1931–1936, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. B. L. Ebert, J. Pretz, J. Bosco et al., “Identification of RPS14 as a 5q- syndrome gene by RNA interference screen,” Nature, vol. 451, no. 7176, pp. 335–339, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. S. R. Ellis and P. E. Gleizes, “Diamond Blackfan anemia: ribosomal proteins going rogue,” Seminars in Hematology, vol. 48, pp. 89–96, 2011. View at Google Scholar
  35. A. Valencia, J. Cervera, E. Such, M. A. Sanz, and G. F. Sanz, “Lack of RPS14 promoter aberrant methylation supports the haploinsufficiency model for the 5q- Syndrome,” Blood, vol. 112, no. 3, p. 918, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. N. Draptchinskaia, P. Gustavsson, B. Andersson et al., “The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia,” Nature Genetics, vol. 21, no. 2, pp. 169–175, 1999. View at Publisher · View at Google Scholar · View at Scopus
  37. H. T. Gazda, A. Grabowska, L. B. Merida-Long et al., “Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia,” American Journal of Human Genetics, vol. 79, no. 6, pp. 1110–1118, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. K. A. Ganapathi and A. Shimamura, “Ribosomal dysfunction and inherited marrow failure,” British Journal of Haematology, vol. 141, no. 3, pp. 376–387, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. M. F. Campagnoli, U. Ramenghi, M. Armiraglio et al., “RPS19 mutations in patients with Diamond-Blackfan anemia,” Human Mutation, vol. 29, no. 7, pp. 911–920, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Cmejla, J. Cmejlova, H. Handrkova et al., “Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11) genes in Czech patients with diamond-blackfan anemia,” Human Mutation, vol. 30, no. 3, pp. 321–327, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. J. M. Lipton and S. R. Ellis, “Diamond-blackfan anemia: diagnosis, treatment, and molecular pathogenesis,” Hematology/Oncology Clinics of North America, vol. 23, no. 2, pp. 261–282, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. L. Doherty, M. R. Sheen, A. Vlachos et al., “Ribosomal protein genes RPS10 and RPS26 are commonly mutated in diamond-blackfan anemia,” American Journal of Human Genetics, vol. 86, no. 2, pp. 222–228, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. E. E. Devlin, L. DaCosta, N. Mohandas, G. Elliott, and D. M. Bodine, “A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia,” Blood, vol. 116, no. 15, pp. 2826–2835, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Hoefele, A. M. Bertrand, M. Stehr et al., “Disorders of sex development and Diamond-Blackfan anemia: is there an association?” Pediatric Nephrology, vol. 25, no. 7, pp. 1255–1261, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. E. Ito, Y. Konno, T. Toki, and K. Terui, “Molecular pathogenesis in Diamond-Blackfan anemia,” International Journal of Hematology, vol. 92, no. 3, pp. 413–418, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. I. Boria, E. Garelli, H. T. Gazda et al., “The ribosomal basis of diamond-blackfan anemia: mutation and database update,” Human Mutation, vol. 31, no. 12, pp. 1269–1279, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. H. W. Josephs, “Anemia of infancy and early childhood,” Medicine, vol. 15, pp. 307–451, 1936. View at Google Scholar
  48. L. K. Diamond and K. D. Blackfan, “Hypoplastic anemia,” Am. J. Dis. Child., vol. 56, pp. 464–467, 1938. View at Google Scholar
  49. J. L. Barlow, L. F. Drynan, D. R. Hewett et al., “A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q-syndrome,” Nature Medicine, vol. 16, no. 1, pp. 59–66, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Pellagatti, E. Hellström-Lindberg, A. Giagounidis et al., “Haploinsufficiency of RPS14 in 5q- syndrome is associated with deregulation of ribosomal- and translation-related genes,” British Journal of Haematology, vol. 142, no. 1, pp. 57–64, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. H. T. Gazda, A. T. Kho, D. Sanoudou et al., “Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia,” Stem Cells, vol. 24, no. 9, pp. 2034–2044, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Sridhar, D. T. Ross, R. Tibshirani, A. J. Butte, and P. L. Greenberg, “Relationship of differential gene expression profiles in CD34+ myelodysplastic syndrome marrow cells to disease subtype and progression,” Blood, vol. 114, no. 23, pp. 4847–4858, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. H. He and Y. Sun, “Ribosomal protein S27L is a direct p53 target that regulates apoptosis,” Oncogene, vol. 26, no. 19, pp. 2707–2716, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Li, J. Tan, L. Zhuang et al., “Ribosomal protein S27-like, a p53-inducible modulator of cell fate in response to genotoxic stress,” Cancer Research, vol. 67, no. 23, pp. 11317–11326, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. M. J. Farquhar and D. T. Bowen, “Oxidative stress and the myelodysplastic syndromes,” International Journal of Hematology, vol. 77, no. 4, pp. 342–350, 2003. View at Google Scholar · View at Scopus
  56. H. Ghoti, J. Amer, A. Winder, E. Rachmilewitz, and E. Fibach, “Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome,” European Journal of Haematology, vol. 79, no. 6, pp. 463–467, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. B. Novotna, Y. Bagryantseva, M. Siskova, and R. Neuwirtova, “Oxidative DNA damage in bone marrow cells of patients with low-risk myelodysplastic syndrome,” Leukemia Research, vol. 33, no. 2, pp. 340–343, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. D. P. Bartel, “MicroRNAs: target recognition and regulatory functions,” Cell, vol. 136, no. 2, pp. 215–233, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. D. T. Starczynowski, F. Kuchenbauer, B. Argiropoulos et al., “Identification of miR-145 and miR-146a as mediators of the 5q-syndrome phenotype,” Nature Medicine, vol. 16, no. 1, pp. 49–58, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. E. Terpos, E. Verrou, A. Banti, V. Kaloutsi, A. Lazaridou, and K. Zervas, “Bortezomib is an effective agent for MDS/MPD syndrome with 5q- anomaly and thrombocytosis,” Leukemia Research, vol. 31, no. 4, pp. 559–562, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. D. T. Starczynowski, R. Morin, A. McPherson et al., “Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations,” Blood, vol. 117, pp. 595–607, 2011. View at Google Scholar
  62. M. Kumar, A. Narla, A. Nonami et al., “Coordinate 1oss of a microRNA and protein-coding gene cooperate in the pathogenesis of 5q- syndrome,” Blood, vol. 118, pp. 4663–4673, 2011. View at Google Scholar
  63. J. Boultwood, A. Pellagatti, A. N. J. McKenzie, and J. S. Wainscoat, “Advances in the 5q-syndrome,” Blood, vol. 116, no. 26, pp. 5803–5811, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. H. Votavova, M. Grmanova, M. Dostalova Merkerova et al., “Differential expression of microRNAs in CD34+ cells of 5q- syndrome,” Journal of Hematology and Oncology, vol. 4, p. 1, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. H. I. Suzuki, K. Yamagata, K. Sugimoto, T. Iwamoto, S. Kato, and K. Miyazono, “Modulation of microRNA processing by p53,” Nature, vol. 460, no. 7254, pp. 529–533, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. L. Boominathan, “The guardians of the genome (p53, TA-p73, and TA-p63) are regulators of tumor suppressor miRNAs network,” Cancer and Metastasis Reviews, vol. 29, no. 4, pp. 613–639, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Ozen, C. J. Creighton, M. Ozdemir, and M. Ittmann, “Widespread deregulation of microRNA expression in human prostate cancer,” Oncogene, vol. 27, no. 12, pp. 1788–1793, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. Y. Wang and C. G. L. Lee, “MicroRNA and cancer—focus on apoptosis,” Journal of Cellular and Molecular Medicine, vol. 13, no. 1, pp. 12–23, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Akao, Y. Nakagawa, and T. Naoe, “MicroRNA-143 and -145 in colon cancer,” DNA and Cell Biology, vol. 26, no. 5, pp. 311–320, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Sachdeva and Y. Y. Mo, “miR-145-mediated suppression of cell growth, invasion and metastasis,” American Journal of Translational Research, vol. 2, no. 2, pp. 170–180, 2010. View at Google Scholar · View at Scopus
  71. J. Zhang, H. Guo, H. Zhang et al., “Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene friend leukemia virus integration 1 gene,” Cancer, vol. 117, no. 1, pp. 86–95, 2011. View at Google Scholar
  72. B. Shi, L. Sepp-Lorenzino, M. Prisco, P. Linsley, T. Deangelis, and R. Baserga, “Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells,” Journal of Biological Chemistry, vol. 282, no. 45, pp. 32582–32590, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Zhang, H. Guo, G. Qian et al., “MiR-145, a new regulator of the DNA Fragmentation Factor-45 (DFF45)-mediated apoptotic network,” Molecular Cancer, vol. 9, article 211, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. C. C. Chiu, C. H. M. Y. Lin, and K. Fang, “Etoposide (VP-16) sensitizes p53-deficient human non-small cell lung cancer cells to caspase-7-mediated apoptosis,” Apoptosis, vol. 10, no. 3, pp. 643–650, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. X. Liu, H. Zou, C. Slaughter, and X. Wang, “DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis,” Cell, vol. 89, no. 2, pp. 175–184, 1997. View at Google Scholar · View at Scopus
  76. A. E. Williams, M. M. Perry, S. A. Moschos, H. M. Larner-Svensson, and M. A. Lindsay, “Role of miRNA-146a in the regulation of the innate immune response and cancer,” Biochemical Society Transactions, vol. 36, no. 6, pp. 1211–1215, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. L. Li, X.-P. Chen, and Y.-J. Li, “MicroRNA-146a and human disease,” Scandinavian Journal of Immunology, vol. 71, pp. 227–231, 2010. View at Google Scholar
  78. D. T. Starczynowski, F. Kuchenbauer, and J. Wegrzyn, “MicroRNA-146a disrupts hematopoietic differentiation and survival,” Experimental Hematology, vol. 39, pp. 167–178, 2011. View at Google Scholar
  79. K. R. Cordes, N. T. Sheehy, M. P. White et al., “MiR-145 and miR-143 regulate smooth muscle cell fate and plasticity,” Nature, vol. 460, no. 7256, pp. 705–710, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Boettger, N. Beetz, S. Kostin et al., “Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster,” Journal of Clinical Investigation, vol. 119, no. 9, pp. 2634–2647, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Dostalova Merkerova, Z. Krejcik, H. Votavova, M. Belickova, A. Vasikova, and J. Cermak, “Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome,” European Journal of Human Genetics, vol. 19, pp. 313–319, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. L. Panić, J. Montagne, M. Cokarić, and S. Volarević, “S6-haploinsufficiency activates the p53 tumor suppressor,” Cell Cycle, vol. 6, no. 1, pp. 20–24, 2007. View at Google Scholar · View at Scopus
  83. N. Danilova, K. M. Sakamoto, and S. Lin, “Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family,” Blood, vol. 112, no. 13, pp. 5228–5237, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. N. C. Jones, M. L. Lynn, K. Gaudenz et al., “Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function,” Nature Medicine, vol. 14, no. 2, pp. 125–133, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. K. A. McGowan, J. Z. Li, C. Y. Park et al., “Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects,” Nature Genetics, vol. 40, no. 8, pp. 963–970, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Barkić, S. Crnomarković, K. Grabušić et al., “The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival,” Molecular and Cellular Biology, vol. 29, no. 10, pp. 2489–2504, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. C. Constantinou, A. Elia, and M. J. Clemens, “Activation of p53 stimulates proteasome-dependent truncation of elF4E-binding protein 1 (4E-BP1),” Biology of the Cell, vol. 100, no. 5, pp. 279–289, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. J. Momand, H. H. Wu, and G. Dasgupta, “MDM2-master regulator of the p53 tumor suppressor protein,” Gene, vol. 242, no. 1-2, pp. 15–29, 2000. View at Publisher · View at Google Scholar · View at Scopus
  89. S. Fang, J. P. Jensen, R. L. Ludwig, K. H. Vousden, and A. M. Weissman, “Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53,” Journal of Biological Chemistry, vol. 275, no. 12, pp. 8945–8951, 2000. View at Publisher · View at Google Scholar · View at Scopus
  90. H. V. Clegg, K. Itahana, and Y. Zhang, “Unlocking the Mdm2-p53 loop: ubiquitin is the key,” Cell Cycle, vol. 7, no. 3, pp. 287–292, 2008. View at Google Scholar · View at Scopus
  91. M. S. Dai and H. Lu, “Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5,” Journal of Biological Chemistry, vol. 279, no. 43, pp. 44475–44482, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. M. A. E. Lohrum, R. L. Ludwig, M. H. G. Kubbutat, M. Hanlon, and K. H. Vousden, “Regulation of HDM2 activity by the ribosomal protein L11,” Cancer Cell, vol. 3, no. 6, pp. 577–587, 2003. View at Publisher · View at Google Scholar · View at Scopus
  93. Y. Zhang, G. W. Wolf, K. Bhat et al., “Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway,” Molecular and Cellular Biology, vol. 23, no. 23, pp. 8902–8912, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. K. P. Bhat, K. Itahana, A. Jin, and Y. Zhang, “Essential role of ribosomal protein L11 in mediating growth inhibition-induced p53 activation,” EMBO Journal, vol. 23, no. 12, pp. 2402–2412, 2004. View at Publisher · View at Google Scholar · View at Scopus
  95. M. S. Dai, S. X. Zeng, Y. Jin, X. X. Sun, L. David, and H. Lu, “Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition,” Molecular and Cellular Biology, vol. 24, no. 17, pp. 7654–7668, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. Y. Ofir-Rosenfeld, K. Boggs, D. Michael, M. B. Kastan, and M. Oren, “Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26,” Molecular Cell, vol. 32, no. 2, pp. 180–189, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. D. Chen, Z. Zhang, M. Li et al., “Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: binding to MDM2, stabilization of p53 protein, and activation of p53 function,” Oncogene, vol. 26, no. 35, pp. 5029–5037, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. Y. Zhang and H. Lu, “Signaling to p53: ribosomal proteins find their way,” Cancer Cell, vol. 16, no. 5, pp. 369–377, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. Y. Zhang, J. Wang, Y. Yuan et al., “Negative regulation of HDM2 to attenuate p53 degradation by ribosomal protein L26,” Nucleic Acids Research, vol. 38, no. 19, Article ID gkq536, pp. 6544–6554, 2010. View at Publisher · View at Google Scholar · View at Scopus
  100. D. G. Pestov, Z. Strezoska, and L. F. Lau, “Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: effects of nucleolar protein Bop1 on G1/S transition,” Molecular and Cellular Biology, vol. 21, no. 13, pp. 4246–4255, 2001. View at Publisher · View at Google Scholar · View at Scopus
  101. C. Deisenroth and Y. Zhang, “Ribosome biogenesis surveillance: probing the ribosomal protein-Mdm2-p53 pathway,” Oncogene, vol. 29, no. 30, pp. 4253–4260, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. D. M. Gilkes, L. Chen, and J. Chen, “MDMX regulation of p53 response to ribosomal stress,” EMBO Journal, vol. 25, no. 23, pp. 5614–5625, 2006. View at Publisher · View at Google Scholar · View at Scopus
  103. X. X. Sun, Y. G. Wang, D. P. Xirodimas, and M. S. Dai, “Perturbation of 60 S ribosomal biogenesis results in ribosomal protein L5- and L11-dependent p53 activation,” Journal of Biological Chemistry, vol. 285, no. 33, pp. 25812–25821, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. A. Pellagatti, T. Marafioti, J. C. Paterson et al., “Induction of p53 and up-regulation of the p53 pathway in the human 5q- syndrome,” Blood, vol. 115, no. 13, pp. 2721–2723, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. M. E. Perry, “The regulation of the p53-mediated stress response by MDM2 and MDM4,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 1, article a000968, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. J. S. L. Ho, W. Ma, D. Y. L. Mao, and S. Benchimol, “p53-dependent transcriptional repression of c-myc is required for G 1 cell cycle arrest,” Molecular and Cellular Biology, vol. 25, no. 17, pp. 7423–7431, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Sachdeva, S. Zhu, F. Wu et al., “p53 represses c-Myc through induction of the tumor suppressor miR-145,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 9, pp. 3207–3212, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Sachdeva and Y. Y. Mo, “p53 and c-myc: how does the cell balance "yin" and "yang"?” Cell Cycle, vol. 8, no. 9, p. 1303, 2009. View at Google Scholar · View at Scopus
  109. A. H. L. Truong, D. Cervi, J. Lee, and Y. Ben-David, “Direct transcriptional regulation of MDM2 by Fli-1,” Oncogene, vol. 24, no. 6, pp. 962–969, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. D. H. Christiansen, M. K. Andersen, and J. Pedersen-Bjergaard, “Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis,” Journal of Clinical Oncology, vol. 19, no. 5, pp. 1405–1413, 2001. View at Google Scholar · View at Scopus
  111. J. Pedersen-Bjergaard, M. K. Andersen, M. T. Andersen, and D. H. Christiansen, “Genetics of therapy-related myelodysplasia and acute myeloid leukemia,” Leukemia, vol. 22, no. 2, pp. 240–248, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. M. Jädersten, L. Saft, A. Pellagatti et al., “Clonal heterogeneity in the 5q- syndrome: P53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression,” Haematologica, vol. 94, no. 12, pp. 1762–1766, 2009. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Jädersten, L. Saft, A. Smith et al., “TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict dinase progression,” Journal of Clinical Oncology, vol. 29, pp. 1971–1979, 2011. View at Google Scholar
  114. C. M. Lim, M. A. Cater, J. F. B. Mercer, and S. La Fontaine, “Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A,” Journal of Biological Chemistry, vol. 281, no. 20, pp. 14006–14014, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. S. R. Patel, J. L. Richardson, H. Schulze et al., “Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes,” Blood, vol. 106, no. 13, pp. 4076–4085, 2005. View at Publisher · View at Google Scholar · View at Scopus
  116. J. E. Italiano Jr., S. Patel-Hett, and J. H. Hartwig, “Mechanics of proplatelet elaboration,” Journal of Thrombosis and Haemostasis, vol. 5, supplement 1, pp. 18–23, 2007. View at Google Scholar
  117. F. He, C. T. Wang, and L. T. Gou, “RNA-binding motif protein RBM22 is required for normal development of zebrafish embryos,” Genetics and Molecular Research, vol. 8, no. 4, pp. 1466–1473, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. S. Grisendi, R. Bernardi, M. Rossi et al., “Role of nucleophosmin in embryonic development and tumorigenesis,” Nature, vol. 437, no. 7055, pp. 147–153, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. S. Grisendi, C. Mecucci, B. Falini, and P. P. Pandolfi, “Nucleophosmin and cancer,” Nature Reviews Cancer, vol. 6, no. 7, pp. 493–505, 2006. View at Publisher · View at Google Scholar · View at Scopus
  120. P. Sportoletti, S. Grisendi, S. M. Majid et al., “Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse,” Blood, vol. 111, no. 7, pp. 3859–3862, 2008. View at Publisher · View at Google Scholar · View at Scopus
  121. G. Cazzaniga, M. G. Dell'Oro, C. Mecucci et al., “Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype,” Blood, vol. 106, no. 4, pp. 1419–1422, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. R. Rau and P. Brown, “Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity,” Hematological Oncology, vol. 27, no. 4, pp. 171–181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. M. J. Walter, “Del(5q): gene dosage matters,” Blood, vol. 110, no. 2, pp. 473–474, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. R. Neuwirtova, O. Fuchs, D. Provaznikova et al., “Fli-1 and EKLF gene expression in patients with MDS 5q- syndrome,” Blood, vol. 114, pp. 1090–1091, 2009, abstract no. 2788, Proceedings of the 51st Annual Meeting of the American Society of Hematology, December 5–8, 2009, New Orleans, La, USA. View at Google Scholar
  125. R. Neuwirtova, O. Fuchs, A. Jonasova et al., “The role of Fli-1 and EKLF gene expression in 5q- syndrome compared to MDS low risk with normal chromosome 5,” in Proceedings of the XXXIII World Congress of the International Society of Hematology, Jerusalem, Israel, abstract no. 114, October 2010.
  126. Y. Ben-David, E. B. Giddens, K. Letwin, and A. Bernstein, “Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1,” Genes and Development, vol. 5, no. 6, pp. 908–918, 1991. View at Google Scholar · View at Scopus
  127. D. K. Watson, F. E. Smyth, D. M. Thompson et al., “The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors,” Cell Growth and Differentiation, vol. 3, no. 10, pp. 705–713, 1992. View at Google Scholar · View at Scopus
  128. D. D. K. Prasad, V. N. Rao, and E. S. P. Reddy, “Structure and expression of human Fli-1 gene,” Cancer Research, vol. 52, no. 20, pp. 5833–5837, 1992. View at Google Scholar · View at Scopus
  129. L. Selleri, M. Giovannini, A. Romo et al., “Cloning of the entire FLI1 gene, disrupted by the Ewing's sarcoma translocation breakpoint on 11q24, in a yeast artificial chromosome,” Cytogenetics and Cell Genetics, vol. 67, no. 2, pp. 129–136, 1994. View at Google Scholar · View at Scopus
  130. J. Starck, N. Cohet, C. Gonnet et al., “Functional cross-antagonism between transcription factors FLI-1 and EKLF,” Molecular and Cellular Biology, vol. 23, no. 4, pp. 1390–1402, 2003. View at Publisher · View at Google Scholar · View at Scopus
  131. M. Eisbacher, M. L. Holmes, A. Newton et al., “Protein-protein interaction between Fli-1 and GATA-1 mediates synergistic expression of megakaryocyte-specific genes through cooperative DNA binding,” Molecular and Cellular Biology, vol. 23, no. 10, pp. 3427–3441, 2003. View at Publisher · View at Google Scholar · View at Scopus
  132. P. Jackers, G. Szalai, O. Moussa, and D. K. Watson, “Ets-dependent regulation of target gene expression during megakaryopoiesis,” Journal of Biological Chemistry, vol. 279, no. 50, pp. 52183–52190, 2004. View at Publisher · View at Google Scholar · View at Scopus
  133. J. L. Svenson, K. Chike-Harris, M. Y. Amria, and T. K. Nowling, “The mouse and human Fli1 genes are similarly regulated by Ets factors in T cells,” Genes and Immunity, vol. 11, no. 2, pp. 161–172, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. J. Starck, A. Doubeikovski, S. Sarrazin et al., “Spi-1/PU.1 Is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines,” Molecular and Cellular Biology, vol. 19, no. 1, pp. 121–135, 1999. View at Google Scholar · View at Scopus
  135. N. Rekhtman, F. Radparvar, T. Evans, and A. I. Skoultchi, “Direct interaction of hematopoietic transcription factors PU.1 and GATA- 1: functional antagonism in erythroid cells,” Genes and Development, vol. 13, no. 11, pp. 1398–1411, 1999. View at Google Scholar · View at Scopus
  136. P. Zhang, X. Zhang, A. Iwama et al., “PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding,” Blood, vol. 96, no. 8, pp. 2641–2648, 2000. View at Google Scholar · View at Scopus
  137. G. Juban, G. Giraud, B. Guyot et al., “Spi-1 and Fli-1 directly activate common target genes involved in ribosome biogenesis in friend erythroleukemic cells,” Molecular and Cellular Biology, vol. 29, no. 10, pp. 2852–2864, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. D. T. Starczynowski and A. Karsan, “Innate immune signaling in the myelodysplastic syndromes,” Hematology/Oncology Clinics of North America, vol. 24, pp. 343–359, 2010. View at Google Scholar
  139. D. R. Hodge, W. Xiao, P. A. Clausen, G. Heidecker, M. Szyf, and W. L. Farrar, “Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erythroleukemia cells,” Journal of Biological Chemistry, vol. 276, no. 43, pp. 39508–39511, 2001. View at Publisher · View at Google Scholar · View at Scopus
  140. D. R. Hodge, D. Li, S. M. Qi, and W. L. Farrar, “IL-6 induces expression of the Fli-1 proto-oncogene via STAT3,” Biochemical and Biophysical Research Communications, vol. 292, pp. 287–291, 2002. View at Google Scholar
  141. M. R. Tallack, T. Whitington, W. S. Yuen et al., “A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells,” Genome Research, vol. 20, no. 8, pp. 1052–1063, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. M. Siatecka and J. J. Bieker, “The multifunctional role of EKLF/KLF1 during erythropoiesis,” Blood, vol. 118, pp. 2044–2054, 2011. View at Google Scholar
  143. L. C. Doré and J. D. Crispino, “Transcription factor in erythroid cell and megakaryocyte development,” Blood, vol. 118, pp. 231–239, 2011. View at Google Scholar
  144. J. Borg, P. Papadopoulos, M. Georgitsi et al., “Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin,” Nature Genetics, vol. 42, no. 9, pp. 801–805, 2010. View at Publisher · View at Google Scholar · View at Scopus
  145. P. Frontelo, D. Manwani, M. Galdass et al., “Novel role for EKLF in megakaryocyte lineage commitment,” Blood, vol. 110, no. 12, pp. 3871–3880, 2007. View at Publisher · View at Google Scholar · View at Scopus
  146. F. Bouilloux, G. Juban, N. Cohet et al., “EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation,” Blood, vol. 112, no. 3, pp. 576–584, 2008. View at Publisher · View at Google Scholar · View at Scopus
  147. O. Klimchenko, M. Mori, A. DiStefano et al., “A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis,” Blood, vol. 114, no. 8, pp. 1506–1517, 2009. View at Publisher · View at Google Scholar · View at Scopus
  148. M. R. Tallack and A. C. Perkins, “Megakaryocyte-erythroid lineage promiscuity in EKLF null mouse blood,” Haematologica, vol. 95, no. 1, pp. 144–147, 2010. View at Publisher · View at Google Scholar · View at Scopus
  149. S. Dutt, A. Narla, K. Lin et al., “Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells,” Blood, vol. 117, no. 9, pp. 2567–2576, 2011. View at Google Scholar
  150. M. Cazzola, “Myelodysplastic syndrome with isolated 5q deletion (5q- syndrome). A clonal stem cell disorder characterized by defective ribosome biogenesis,” Haematologica, vol. 93, no. 7, pp. 967–972, 2008. View at Publisher · View at Google Scholar · View at Scopus
  151. J. L. Barlow, L. F. Drynan, N. L. Trim, W. N. Erber, A. J. Warren, and A. N. J. McKenzie, “New insights into 5q- syndrome as a ribosomopathy,” Cell Cycle, vol. 9, no. 21, pp. 4286–4293, 2010. View at Publisher · View at Google Scholar · View at Scopus
  152. Y. Liu, S. E. Elf, Y. Miyata et al., “p53 regulates hematopoietic stem cell quiescence,” Cell Stem Cell, vol. 4, no. 1, pp. 37–48, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. Y. Liu, S. E. Elf, T. Asai et al., “The p53 tumor suppressor protein is a critical regulator of hematopoietic stem cell behavior,” Cell Cycle, vol. 8, no. 19, pp. 3120–3124, 2009. View at Google Scholar · View at Scopus
  154. E. Wattel, C. Preudhomme, B. Hecquet et al., “p53 Mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies,” Blood, vol. 84, no. 9, pp. 3148–3157, 1994. View at Google Scholar · View at Scopus
  155. Y. Kita-Sasai, S. Horiike, S. Misawa et al., “International prognostic scoring system and TP53 mutations are independent prognostic indicators for patients with myelodysplastic syndrome,” British Journal of Haematology, vol. 115, no. 2, pp. 309–312, 2001. View at Publisher · View at Google Scholar · View at Scopus
  156. S. Horiike, Y. Kita-Sasai, M. Nakao, and M. Taniwaki, “Configuration of the TP53 gene as an independent prognostic parameter of myelodysplastic syndrome,” Leukemia and Lymphoma, vol. 44, no. 6, pp. 915–922, 2003. View at Publisher · View at Google Scholar · View at Scopus
  157. L. Garderet, L. Kobari, C. Mazurier et al., “Unimpaired terminal erythroid differentiation and preserved enucleation capacity in myelodysplastic 5q(del) clones: a single cell study,” Haematologica, vol. 95, no. 3, pp. 398–405, 2010. View at Publisher · View at Google Scholar · View at Scopus
  158. T. M. A. Neildez-Nguyen, H. Wajcman, M. C. Marden et al., “Human erythroid cells produced ex vivo at large scale differentiate into red blood cells in vivo,” Nature Biotechnology, vol. 20, no. 5, pp. 467–472, 2002. View at Publisher · View at Google Scholar · View at Scopus
  159. M. C. Giarratana, L. Kobari, H. Lapillonne et al., “Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells,” Nature Biotechnology, vol. 23, no. 1, pp. 69–74, 2005. View at Publisher · View at Google Scholar · View at Scopus
  160. M. Jädersten, “Pathophysiology and treatment of the myelodysplastic syndrome with isolated 5q deletion,” Haematologica, vol. 95, no. 3, pp. 348–351, 2010. View at Publisher · View at Google Scholar · View at Scopus
  161. M. Virgilio, E. Payne, A. Narla et al., “Treatment of zebrafish models of ribosomopathies (Diamond Blackfan anemia (DBA) and 5q-syndrome with Lleucine results in an improvement of anemia and development defects: evidence for a common pathway,” Blood, vol. 116, abstract 195, pp. 89–90, 2010. View at Google Scholar
  162. J. Cmejlova, L. Dolezalova, D. Pospisilova, K. Petrtylova, J. Petrak, and R. Cmejla, “Translational efficiency in patients with Diamond-Blackfan anemia,” Haematologica, vol. 91, no. 11, pp. 1456–1464, 2006. View at Google Scholar · View at Scopus
  163. J. C. Anthony, T. G. Anthony, S. R. Kimball, T. C. Vary, and L. S. Jefferson, “Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased elF4F formation,” Journal of Nutrition, vol. 130, no. 2, pp. 139–145, 2000. View at Google Scholar · View at Scopus
  164. C. J. Lynch, B. J. Patson, J. Anthony et al., “Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue,” American Journal of Physiology, vol. 283, pp. E506–E513, 2002. View at Google Scholar
  165. L. E. Norton and D. K. Layman, “Leucine regulates translation initiation of protein synthesis in skeletal muscle after excercise,” Journal of Nutrition, vol. 136, pp. 533S–537S, 2006. View at Google Scholar
  166. J. Escobar, J. W. Frank, A. Suryawan et al., “Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle,” American Journal of Physiology, vol. 293, pp. E1615–E1621, 2007. View at Google Scholar
  167. D. Pospisilova, J. Cmejlova, J. Hak, T. Adam, and R. Cmejla, “Successful treatment of a Diamond-Blackfan anemia patient with amino acid leucine,” Haematologica, vol. 92, no. 5, pp. e66–67, 2007. View at Publisher · View at Google Scholar · View at Scopus
  168. A. List, G. Dewald, J. Bennett et al., “Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion,” The New England Journal of Medicine, vol. 355, no. 14, pp. 1456–1465, 2006. View at Publisher · View at Google Scholar · View at Scopus
  169. M. Melchert, V. Kale, and A. List, “The role of lenalidomide in the treatment of patients with chromosome 5q deletion and other myelodysplastic syndromes,” Current Opinion in Hematology, vol. 14, no. 2, pp. 123–129, 2007. View at Publisher · View at Google Scholar · View at Scopus
  170. A. F. List, “Lenalidomide—the phoenix rises,” The New England Journal of Medicine, vol. 357, no. 21, pp. 2183–2186, 2007. View at Publisher · View at Google Scholar · View at Scopus
  171. S. Kurtin and A. List, “Durable long-term responses in patients with myelodysplastic syndromes treated with lenalidomide,” Clinical Lymphoma and Myeloma, vol. 9, no. 3, pp. E10–E13, 2009. View at Publisher · View at Google Scholar · View at Scopus
  172. R. S. Komrojki and A. F. List, “Lenalidomide for teatment of myelodysplastic syndromes: current status and future directions,” Hematology/Oncology Clinics of North America, vol. 24, pp. 377–388, 2010. View at Google Scholar
  173. S. M. Post and A. Quintás-Cardama, “Closing in on the pathogenesis of the 5q- syndrome,” Expert Review of Anticancer Therapy, vol. 10, no. 5, pp. 655–658, 2010. View at Publisher · View at Google Scholar · View at Scopus
  174. A. Raza, J. A. Reeves, E. J. Feldman et al., “Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q,” Blood, vol. 111, no. 1, pp. 86–93, 2008. View at Publisher · View at Google Scholar · View at Scopus
  175. B. L. Ebert, N. Galili, P. Tamayo et al., “An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome,” PLoS Medicine, vol. 5, no. 2, pp. 0312–0322, 2008. View at Publisher · View at Google Scholar · View at Scopus
  176. C. Chen, D. T. Bowen, A. A. N. Giagounidis, B. Schlegelberger, S. Haase, and E. G. Wright, “Identification of disease- and therapy-associated proteome changes in the sera of patients with myelodysplastic syndromes and del(5q),” Leukemia, vol. 24, no. 11, pp. 1875–1884, 2010. View at Publisher · View at Google Scholar · View at Scopus
  177. S. Wei, X. Chen, K. Rocha et al., “A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 31, pp. 12974–12979, 2009. View at Publisher · View at Google Scholar · View at Scopus
  178. S. H. Kimura and H. Nojima, “Cyclin G1 associates with MDM2 and regulates accumulation and degradation of p53 protein,” Genes to Cells, vol. 7, no. 8, pp. 869–880, 2002. View at Publisher · View at Google Scholar · View at Scopus
  179. X. K. Zhang and D. K. Watson, “The FLI-1 transcription factor is a short-lived phosphoprotein in T cells,” Journal of Biochemistry, vol. 137, no. 3, pp. 297–302, 2005. View at Publisher · View at Google Scholar · View at Scopus
  180. J. B. Bartlett, K. Dredge, and A. G. Dalgleish, “The evolution of thalidomide and its IMiD derivatives as anticancer agents,” Nature Reviews Cancer, vol. 4, no. 4, pp. 314–322, 2004. View at Google Scholar · View at Scopus
  181. A. Pellagatti, M. Jädersten, A. M. Forsblom et al., “Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 27, pp. 11406–11411, 2007. View at Publisher · View at Google Scholar · View at Scopus
  182. E. N. Oliva, M. Cuzzola, F. Nobile et al., “Changes in RPS14 expression levels during lenalidomide treatment in Low- and Intermediate-1-risk myelodysplastic syndromes with chromosome 5q deletion,” European Journal of Haematology, vol. 85, no. 3, pp. 231–235, 2010. View at Publisher · View at Google Scholar · View at Scopus
  183. C. P. Venner, A. F. List, T. J. Nevill et al., “Induction of micro RNA-143 and 145 in pre-treatment CD34+ cells from patients with myelodysplastic syndrome (MDS) after in vitro exposure to lenalidomide correlates with clinical response in patients harboring the del5q abnormality,” Blood, vol. 116, abstract 123, p. 60, 2010. View at Google Scholar
  184. M. Ximeri, A. Galanopoulos, M. Klaus et al., “Effect of lenalidomide therapy on hematopoiesis of patients with myelodysplastic syndrome associated with chromosome 5q deletion,” Haematologica, vol. 95, no. 3, pp. 406–414, 2010. View at Publisher · View at Google Scholar · View at Scopus
  185. R. Tehranchi, P. S. Woll, K. Anderson et al., “Persistent malignant stem cells in del(5q) myelodysplasia in remission,” The New England Journal of Medicine, vol. 363, no. 11, pp. 1025–1037, 2010. View at Publisher · View at Google Scholar · View at Scopus