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 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.
Riva
Giovanni
G
Section of Hematology, Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Via Del Pozzo 71, Modena, Italy.
Luppi
Mario
M
Barozzi
Patrizia
P
Quadrelli
Chiara
C
Basso
Sabrina
S
Vallerini
Daniela
D
Zanetti
Eleonora
E
Morselli
Monica
M
Forghieri
Fabio
F
Maccaferri
Monica
M
Volzone
Francesco
F
Del Giovane
Cinzia
C
D'Amico
Roberto
R
Locatelli
Franco
F
Torelli
Giuseppe
G
Comoli
Patrizia
P
Potenza
Leonardo
L
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
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