Targeting chemokines for acute lymphoblastic leukemia therapy

J Hematol Oncol. 2021 Mar 20;14(1):48. doi: 10.1186/s13045-021-01060-y.

Abstract

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the malignant clonal expansion of lymphoid hematopoietic precursors. It is regulated by various signaling molecules such as cytokines and adhesion molecules in its microenvironment. Chemokines are chemotactic cytokines that regulate migration, positioning and interactions of cells. Many chemokine axes such as CXCL12/CXCR4 and CCL25/CCR9 have been proved to play important roles in leukemia microenvironment and further affect ALL outcomes. In this review, we summarize the chemokines that are involved in ALL progression and elaborate on their roles and mechanisms in leukemia cell proliferation, infiltration, drug resistance and disease relapse. We also discuss the potential of targeting chemokine axes for ALL treatments, since many related inhibitors have shown promising efficacy in preclinical trials, and some of them have entered clinical trials.

Keywords: Acute lymphoblastic leukemia; Chemokine; Microenvironment; Therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Chemokine CXCL12 / metabolism
  • Chemokines / metabolism*
  • Disease Progression
  • Drug Discovery
  • Humans
  • Molecular Targeted Therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Receptors, CXCR4 / metabolism
  • Tumor Microenvironment / drug effects*

Substances

  • Antineoplastic Agents
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Chemokines
  • Receptors, CXCR4