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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
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
- Source :
- Blood. 115:1512-1518
- Publication Year :
- 2010
- Publisher :
- American Society of Hematology, 2010.
-
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 p190BCR-ABL–specific T cells in the bone marrow and peripheral blood. p190BCR-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-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.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Male
Time Factors
Immunology
Fusion Proteins, bcr-abl
Antineoplastic Agents
Bone Marrow Cells
Biology
Biochemistry
Piperazines
Interferon-gamma
Recurrence
hemic and lymphatic diseases
Acute lymphocytic leukemia
medicine
Humans
Cytotoxic T cell
Aged
Aged, 80 and over
Myeloid leukemia
Imatinib
Cell Biology
Hematology
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease
Minimal residual disease
Leukemia
Pyrimidines
Imatinib mesylate
medicine.anatomical_structure
Benzamides
Imatinib Mesylate
Cancer research
Interleukin-2
BCR-ABL-specific T lymphocytes
Philadelphia chromosome-positive acute lymphoblastic leukemia
Female
Bone marrow
Immunologic Memory
Follow-Up Studies
T-Lymphocytes, Cytotoxic
medicine.drug
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....b06d42cf52de9834d992f7820fe38c53
- Full Text :
- https://doi.org/10.1182/blood-2009-06-230391