title: 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 high-dose imatinib mesylate maintenance underwent long-term immunological monitoring (range, 2-65 months) of (p190)BCR-ABL-specific T cells in the bone marrow and peripheral blood. (p190)BCR-ABL-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-gamma, tumor necrosis factor-alpha, 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 (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.
authors.affiliation: Section of Hematology, Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Via Del Pozzo 71, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Riva
authors.forename: Mario
authors.initials: M
authors.lastname: Luppi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Barozzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Quadrelli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Basso
authors.forename: Daniela
authors.initials: D
authors.lastname: Vallerini
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zanetti
authors.forename: Monica
authors.initials: M
authors.lastname: Morselli
authors.forename: Fabio
authors.initials: F
authors.lastname: Forghieri
authors.forename: Monica
authors.initials: M
authors.lastname: Maccaferri
authors.forename: Francesco
authors.initials: F
authors.lastname: Volzone
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Torelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.forename: Leonardo
authors.initials: L
authors.lastname: Potenza
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D001854:Bone Marrow Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006801:Humans; D000068877:Imatinib Mesylate; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology*; D011743:Pyrimidines / Q000008:administration & dosage*; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C508594:IL2 protein, human; D007376:Interleukin-2; D010879:Piperazines; D011743:Pyrimidines; D007371:Interferon-gamma; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl