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.

Imatinib mesylate (IM) has been demonstrated to be permissive for the emergence of T cells directed against chronic myeloid leukemia cells. Ten Philadelphia chromosome-positive acute lymphoblastic leukemia patients, receiving high dose IM maintenance, underwent a long-term immunological monitoring (range 2-65 months) of (p190)BCR-ABL-specific T cells in the bone marrow (BM) and peripheral blood (PB). (p190)BCR-ABL-specific T lymphocytes were detected in all patients, more frequently in BM than in PB samples (67% vs 25%, p<0.01), and resulted significantly associated with lower minimal residual disease values (p<0.001), while absent at leukemia relapse. Specific T cells were mainly effector memory CD8+ and CD4+ T cells, producing IFNgamma, TNFalpha and IL-2 (median % positive cells: 3.34, 3.04, 3.58, respectively). Cytotoxic subsets able to lyse BCR-ABL-positive leukemia blasts were also detectable. Whether these autologous (p190)BCR-ABL-specific T cells may be detectable under other tyrosine-kinase inhibitors, expanded ex vivo and exploited for immunotherapy remains to be addressed.