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Journal of Immunology Research
Volume 2019, Article ID 5601396, 11 pages
Review Article

Notch/CXCR4 Partnership in Acute Lymphoblastic Leukemia Progression

1Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Roma, Italy
2Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, Italy

Correspondence should be addressed to Maria Pia Felli; ti.1amorinu@illef.aipairam

Received 30 November 2018; Revised 21 May 2019; Accepted 12 June 2019; Published 27 June 2019

Academic Editor: Enrique Ortega

Copyright © 2019 Georgia Tsaouli et al. 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.


Acute lymphoblastic leukemia (ALL) is the most common cancer among children. Recent advances in chemotherapy have made ALL a curable hematological malignancy. In children, there is 25% chance of disease relapse, typically in the central nervous system. While in adults, there is a higher chance of relapse. ALL may affect B-cell or T-cell lineages. Different genetic alterations characterize the two ALL forms. Deregulated Notch, either Notch1 or Notch3, and CXCR4 receptor signaling are involved in ALL disease development and progression. By analyzing their relevant roles in the pathogenesis of the two ALL forms, new molecular mechanisms able to modulate cancer cell invasion may be visualized. Notably, the partnership between Notch and CXCR4 may have considerable implications in understanding the complexity of T- and B-ALL. These two receptor pathways intersect other critical signals in the proliferative, differentiation, and metabolic programs of lymphocyte transformation. Also, the identification of the crosstalks in leukemia-stroma interaction within the tumor microenvironment may unveil new targetable mechanisms in disease relapse. Further studies are required to identify new challenges and opportunities to develop more selective and safer therapeutic strategies in ALL progression, possibly contributing to improve conventional hematological cancer therapy.