Emergence of BCR-ABL-specific cytotoxic T cells in the bone marrow of patients with Ph+ acute lymphoblastic leukemia during long-term imatinib mesylate treatment

Abstract

Imatinib mesylate has been demonstrated to allow the emergence of T cells directed against chronic myeloid leukemia cells. A total of 10 Philadelphia chromosome - positive acute lymphoblastic leukemia patients receiving highdose imatinib mesylate maintenance underwent long-term immunological monitoring (range, 2-65 months) of p190BCR-ABL - specific T cells in the bone marrow and peripheral blood. p190BCRABL - specific T lymphocytes were detected in all patients, more frequently in bone marrow than in peripheral blood samples (67% vs 25%, P < .01) and resulted significantly associated with lower minimal residual disease values (P < .001), whereas absent at leukemia relapse. Specific T cells were mainly effector memory CD8+ and CD4+ T cells, producing interferon-γ, tumor necrosis factor-α, and interleukin-2 (median percentage of positive cells: 3.34, 3.04, and 3.58, respectively). Cytotoxic subsets able to lyse BCR-ABL - positive leukemia blasts also were detectable. Whether these autologous p190BCR-ABL - specific T cells may be detectable under other tyrosine-kinase inhibitors, expanded ex vivo, and exploited for immunotherapy remains to be addressed. © 2010 by The American Society of Hematology.