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

Giovanni Riva, Mario Luppi, Patrizia Barozzi, Chiara Quadrelli, Sabrina Basso, Daniela Vallerini, Eleonora Zanetti, Monica Morselli, Fabio Forghieri, Monica Maccaferri, Francesco Volzone, Cinzia Del Giovane, Roberto D'Amico, Franco Locatelli, Giuseppe Torelli, Patrizia Comoli, Leonardo Potenza

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1512-1518
Number of pages7
JournalBlood
Volume115
Issue number8
DOIs
Publication statusPublished - Feb 25 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Riva, G., Luppi, M., Barozzi, P., Quadrelli, C., Basso, S., Vallerini, D., Zanetti, E., Morselli, M., Forghieri, F., Maccaferri, M., Volzone, F., Del Giovane, C., D'Amico, R., Locatelli, F., Torelli, G., Comoli, P., & Potenza, L. (2010). 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. Blood, 115(8), 1512-1518. https://doi.org/10.1182/blood-2009-06-230391