Imatinib sensitizes T-cell lymphocytes from chronic myeloid leukemia patients to FasL-induced cell death: a brief communication.
There is now substantial evidence that imatinib may affect immune responses, especially those mediated by T lymphocytes. Fas (CD95/Apo-1), a cell death receptor, is a key regulator of the immune system. We have explored the consequences of treatment on the Fas system in chronic myeloid leukemia patients treated with imatinib. In comparison with healthy controls, we found not only a mild blood lymphopenia but also impairment of phytohemagglutinin activation in CD4Fas and CD8Fas lymphocytes of imatinib-treated patients. Moreover, these lymphocyte populations were more sensitive to FasL-induced cell death in relation to an increase in Fas expression at the cell surface. Taken together, these results reveal the role of Fas receptor in the lymphopenia observed in patients treated with imatinib, with potential deleterious consequences on antileukemic responses against this immunogenic hematological malignancy.
CNRS, Institute of Developmental Biology and Cancer Research Université de Nice, France. legros@unice.fr
Laurence
L
Legros
Nathalie
N
Ebran
Emmanuelle
E
Stebe
Philippe
P
Rousselot
Delphine
D
Rea
Jill Patrice
JP
Cassuto
Francois-Xavier
FX
Mahon
Anne-Odile
AO
Hueber
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001549:Benzamides; D002469:Cell Separation; D053222:Fas Ligand Protein / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D019014:fas Receptor / Q000276:immunology
D000970:Antineoplastic Agents; D001549:Benzamides; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D010879:Piperazines; D011743:Pyrimidines; D019014:fas Receptor; D000068877:Imatinib Mesylate