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International Journal of Genomics
Volume 2017, Article ID 6934183, 6 pages
https://doi.org/10.1155/2017/6934183
Review Article

Insights on Genomic and Molecular Alterations in Multiple Myeloma and Their Incorporation towards Risk-Adapted Treatment Strategy: Concise Clinical Review

1Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
2Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

Correspondence should be addressed to Taiga Nishihori; gro.ttiffom@irohihsin.agiat

Received 17 October 2016; Accepted 10 January 2017; Published 8 November 2017

Academic Editor: Lam C. Tsoi

Copyright © 2017 Taiga Nishihori and Kenneth Shain. 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. A. Palumbo and K. Anderson, “Multiple myeloma,” New England Journal of Medicine, vol. 364, no. 11, pp. 1046–1060, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. P. Broderick, D. Chubb, D. C. Johnson et al., “Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk,” Nature Genetics, vol. 44, no. 1, pp. 58–61, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. L. López-Corral, N. C. Gutiérrez, M. B. Vidriales et al., “The progression from MGUS to smoldering myeloma and eventually to multiple myeloma involves a clonal expansion of genetically abnormal plasma cells,” Clinical Cancer Research, vol. 17, no. 7, pp. 1692–1700, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. N. Weinhold, D. C. Johnson, A. C. Rawstron et al., “Inherited genetic susceptibility to monoclonal gammopathy of unknown significance,” Blood, vol. 123, no. 16, pp. 2513–2517, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. S. K. Kumar, S. V. Rajkumar, A. Dispenzieri et al., “Improved survival in multiple myeloma and the impact of novel therapies,” Blood, vol. 111, no. 5, pp. 2516–2520, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. K. H. Shain and W. S. Dalton, “Environmental-mediated drug resistance: a target for multiple myeloma therapy,” Expert Review of Hematology, vol. 2, no. 6, pp. 649–662, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. K. H. Shain, W. S. Dalton, and J. Tao, “The tumor microenvironment shapes hallmarks of mature B-cell malignancies,” Oncogene, vol. 34, no. 36, pp. 4673–4682, 2015. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Fonseca, P. L. Bergsagel, J. Drach et al., “International myeloma working group molecular classification of multiple myeloma: spotlight review,” Leukemia, vol. 23, no. 12, pp. 2210–2221, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Fonseca, E. Blood, M. Rue et al., “Clinical and biologic implications of recurrent genomic aberrations in myeloma,” Blood, vol. 101, no. 11, pp. 4569–4575, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Avet-Loiseau, M. Attal, P. Moreau et al., “Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome,” Blood, vol. 109, no. 8, pp. 3489–3495, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Chesi, E. Nardini, R. S. C. Lim, K. D. Smith, W. Michael Kuehl, and P. L. Bergsagel, “The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts,” Blood, vol. 92, no. 9, pp. 3025–3034, 1998. View at Google Scholar · View at Scopus
  12. M. Chesi, E. Nardini, L. A. Brents et al., “Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3,” Nature Genetics, vol. 16, no. 3, pp. 260–264, 1997. View at Publisher · View at Google Scholar · View at Scopus
  13. H. Avet-Loiseau, T. Facon, B. Grosbois et al., “Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation,” Blood, vol. 99, no. 6, pp. 2185–2191, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. W. M. Kuehl and P. L. Bergsagel, “Multiple myeloma: evolving genetic events and host interactions,” Nature Reviews Cancer, vol. 2, no. 3, pp. 175–187, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. E. Ziv, E. Dean, D. Hu et al., “Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients,” Nature Communications, vol. 6, article 7539, 2015. View at Google Scholar
  16. J. D. Shaughnessy Jr., F. Zhan, B. E. Burington et al., “Avalidated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1,” Blood, vol. 109, no. 6, pp. 2276–2284, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. J. R. Sawyer, G. Tricot, S. Mattox, S. Jagannath, and B. Barlogie, “Jumping translocations of chromosome 1q in multiple myeloma: evidence for a mechanism involving decondensation of pericentromeric heterochromatin,” Blood, vol. 91, no. 5, pp. 1732–1741, 1998. View at Google Scholar · View at Scopus
  18. F. Bock, G. Lu, S. A. Srour et al., “Outcome of patients with multiple myeloma and CKS1B gene amplification after autologous hematopoietic stem cell transplantation,” Biology of Blood and Marrow Transplantation, vol. 22, no. 12, pp. 2159–2164, 2016. View at Publisher · View at Google Scholar
  19. R. Fonseca, S. A. Van Wier, W. J. Chng et al., “Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma,” Leukemia, vol. 20, no. 11, pp. 2034–2040, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Moreau, M. Attal, F. Garban et al., “Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials,” Leukemia, vol. 21, no. 9, pp. 2020–2024, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Kumar, R. Fonseca, R. P. Ketterling et al., “Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics,” Blood, vol. 119, no. 9, pp. 2100–2105, 2012. View at Publisher · View at Google Scholar
  22. S. Roychowdhury, M. K. Iyer, D. R. Robinson et al., “Personalized oncology through integrative high-throughput sequencing: a pilot study,” Science Translational Medicine, vol. 3, no. 111, Article ID 111ra121, 2011. View at Publisher · View at Google Scholar
  23. P. R. Greipp, J. S. Miguel, B. G. M. Dune et al., “International staging system for multiple myeloma,” Journal of Clinical Oncology, vol. 23, no. 15, pp. 3412–3420, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. W. J. Chng, A. Dispenzieri, C.-S. Chim et al., “IMWG consensus on risk stratification in multiple myeloma,” Leukemia, vol. 28, no. 2, pp. 269–277, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Palumbo, H. Avet-Loiseau, S. Oliva et al., “Revised international staging system for multiple myeloma: a report from international myeloma working group,” Journal of Clinical Oncology, vol. 33, no. 26, pp. 2863–2869, 2015. View at Publisher · View at Google Scholar · View at Scopus
  26. R. van Laar, R. A. Bender, A. Zielinski, K. Leigh, B. Barlogie, and G. J. Morgan, “Use of multiple myeloma 70-gene prognostic risk score as a continuous predicitor of patient outcome,” Blood, vol. 128, no. 22, p. 5614, 2016. View at Google Scholar
  27. O. Decaux, L. Lodé, F. Magrangeas et al., “Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: A Study of The Intergroupe Francophone du Myélome,” Journal of Clinical Oncology, vol. 26, no. 29, pp. 4798–4805, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. F. Zhan, Y. Huang, S. Colla et al., “The molecular classification of multiple myeloma,” Blood, vol. 108, no. 6, pp. 2020–2028, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Broyl, D. Hose, H. Lokhorst et al., “Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients,” Blood, vol. 116, no. 14, pp. 2543–2553, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. W. J. Chng, E. Braggio, G. Mulligan et al., “The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition,” Blood, vol. 111, no. 3, pp. 1603–1609, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. N. J. Dickens, B. A. Walker, P. E. Leone et al., “Homozygous deletion mapping in myeloma samples identifies genes and an expression signature relevant to pathogenesis and outcome,” Clinical Cancer Research, vol. 16, no. 6, pp. 1856–1864, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Moreaux, B. Klein, R. Bataille et al., “A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines,” Haematologica, vol. 96, no. 4, pp. 574–582, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. D. Hose, T. Rème, T. Hielscher et al., “Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma,” Haematologica, vol. 96, no. 1, pp. 87–95, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Kuiper, A. Broyl, Y. De Knegt et al., “A gene expression signature for high-risk multiple myeloma,” Leukemia, vol. 26, no. 11, pp. 2406–2413, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. T.-H. Chung, G. Mulligan, R. Fonseca, and W. J. Chng, “A novel measure of chromosome instability can account for prognostic difference in multiple myeloma,” PLoS ONE, vol. 8, no. 6, Article ID e66361, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. L. Shi, G. Campbell, W. D. Jones et al., “The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models,” Nature Biotechnology, vol. 28, no. 8, pp. 827–838, 2010. View at Publisher · View at Google Scholar
  37. T. Meißner, A. Seckinger, T. Rème et al., “Gene expression profiling in multiple myeloma—reporting of entities, risk, and targets in clinical routine,” Clinical Cancer Research, vol. 17, no. 23, pp. 7240–7247, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. D. Hose, T. Rème, T. Meissner et al., “Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma,” Blood, vol. 113, no. 18, pp. 4331–4340, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. K. C. Anderson, M. Alsina, D. Atanackovic et al., “NCCN guidelines insights: multiple myeloma, version 3.2016,” JNCCN Journal of the National Comprehensive Cancer Network, vol. 14, no. 4, pp. 389–400, 2016. View at Google Scholar · View at Scopus
  40. J. R. Mikhael, D. Dingli, V. Roy et al., “Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013,” Mayo Clinic Proceedings, vol. 88, no. 4, pp. 360–376, 2013. View at Publisher · View at Google Scholar
  41. J. F. San Miguel, R. Schlag, N. K. Khuageva et al., “Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma,” New England Journal of Medicine, vol. 359, no. 9, pp. 906–917, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Cavo, P. Tacchetti, F. Patriarca et al., “Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study,” The Lancet, vol. 376, no. 9758, pp. 2075–2085, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. P. Sonneveld, H. Goldschmidt, L. Rosiñol et al., “Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, vol. 31, no. 26, pp. 3279–3287, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Avet-Loiseau, X. Leleu, M. Roussel et al., “Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p),” Journal of Clinical Oncology, vol. 28, no. 30, pp. 4630–4634, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Neben, H. M. Lokhorst, A. Jauch et al., “Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p,” Blood, vol. 119, no. 4, pp. 940–948, 2012. View at Publisher · View at Google Scholar · View at Scopus
  46. J. D. Shaughnessy, Y. Zhou, J. Haessler et al., “TP53 deletion is not an adverse feature in multiple myeloma treated with total therapy 3,” British Journal of Haematology, vol. 147, no. 3, pp. 347–351, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. G. J. Morgan, W. M. Gregory, F. E. Davies et al., “The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis,” Blood, vol. 119, no. 1, pp. 7–15, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. H. Avet-Loiseau, R. Fonseca, D. Siegel et al., “Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma,” Blood, vol. 128, no. 9, pp. 1174–1180, 2016. View at Publisher · View at Google Scholar
  49. M. A. Dimopoulos, K. C. Weise, K. W. Song et al., “Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone,” Haematologica, vol. 100, no. 10, pp. 1327–1333, 2015. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Z. Usmani, Q. Zhang, K. Stratton et al., “Phase II study of pomalidomide in high-risk relapsed and refractory multiple myeloma,” Leukemia, vol. 28, no. 12, pp. 2413–2415, 2014. View at Publisher · View at Google Scholar · View at Scopus
  51. K. A. Noonan, C. A. Huff, J. Davis et al., “Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma,” Science Translational Medicine, vol. 7, no. 288, Article ID 288ra278, 2015. View at Publisher · View at Google Scholar · View at Scopus
  52. M. A. Chapman, M. S. Lawrence, J. J. Keats et al., “Initial genome sequencing and analysis of multiple myeloma,” Nature, vol. 471, no. 7339, pp. 467–472, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. N. Bolli, H. Avet-Loiseau, D. C. Wedge et al., “Heterogeneity of genomic evolution and mutational profiles in multiple myeloma,” Nature Communications, vol. 5, article 2997, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Lohr, P. Stojanov, S. Carter et al., “Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy,” Cancer Cell, vol. 25, no. 1, pp. 91–101, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. B. A. Walker, E. M. Boyle, C. P. Wardell et al., “Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed myeloma,” Journal of Clinical Oncology, vol. 33, no. 33, pp. 3911–3920, 2015. View at Publisher · View at Google Scholar · View at Scopus
  56. G. Mulligan, D. I. Lichter, A. D. Bacco et al., “Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy,” Blood, vol. 123, no. 5, pp. 632–639, 2014. View at Publisher · View at Google Scholar · View at Scopus