T cell acute lymphoblastic leukemia (T-ALL): New insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies

Blood Rev. 2018 Jan;32(1):36-51. doi: 10.1016/j.blre.2017.08.006. Epub 2017 Aug 15.


T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15% and 25% of total childhood and adult ALL cases, respectively. During T-ALL, patients are at risk of organ infiltration by leukemic T-cells. Infiltration is a major consequence of disease relapse and correlates with poor prognosis. Transendothelial migration of leukemic cells is required to exit the blood stream into target organs. While mechanisms of normal T-cell transmigration are well known, the mechanisms of leukemic T-cell extravasation remain elusive; but involvement of chemokines, integrins and Notch signaling play critical roles. Here, we summarize current knowledge about molecular mechanisms of leukemic T-cell infiltration with special emphasis on the newly identified subtype early T-cell-progenitor (ETP)-ALL. Furthermore, we compare the extravasation potential of T-ALL cells with that of other hematologic malignancies such as B-ALL and acute myeloid leukemia (AML).

Keywords: CXCL12; CXCR4; Central nervous system; Diapedesis; Endothelial transmigration; LFA-1; Selectin; T-cells; VLA-4.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers
  • Bone Marrow / pathology
  • Hematologic Neoplasms / etiology
  • Hematologic Neoplasms / metabolism
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / etiology*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Thymus Gland / pathology
  • Tumor Microenvironment


  • Biomarkers