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T cell acute lymphoblastic leukemia (T-ALL): New insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies
Authors:Eduardo Vadillo  Elisa Dorantes-Acosta  Rosana Pelayo  Michael Schnoor
Institution:1. Department for Molecular Biomedicine, Centre for Investigation and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), 07360 Mexico City, Mexico;2. Leukemia Clinic, Children''s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico;3. Oncology Research Unit, National Medical Center, Mexican Institute for Social Security, 06720 Mexico City, Mexico
Abstract: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:Diapedesis  T-cells  Central nervous system  Endothelial transmigration  CXCR4  CXCL12  LFA-1  VLA-4  Selectin
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