Notch/CXCR4 Partnership in Acute Lymphoblastic Leukemia Progression

J Immunol Res. 2019 Jun 27;2019:5601396. doi: 10.1155/2019/5601396. eCollection 2019.


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.

Publication types

  • Review

MeSH terms

  • Adult
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Chemokine CXCL12 / metabolism
  • Child
  • Disease Progression
  • Humans
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / metabolism
  • Receptor, Notch3 / genetics*
  • Receptor, Notch3 / metabolism
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction / genetics
  • Tumor Microenvironment / immunology


  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • NOTCH1 protein, human
  • NOTCH3 protein, human
  • Receptor, Notch1
  • Receptor, Notch3
  • Receptors, CXCR4