Cytotoxic T cells overcome BCR-ABL-mediated resistance to apoptosis.
Chronic myeloid leukemia is a disease marked by expanded clonal hematopoiesis; it is incurable by chemotherapy or radiation but is cured in a majority of patients receiving bone marrow transplantation from nonidentical sibling donors, an outcome generally attributed to a T cell-mediated graft-versus-leukemia effect. In this report, we examine the effect of the P210BCR-ABL fusion protein of the BCR-ABL oncogene, the molecular hallmark of chronic myelogenous leukemia, on the sensitivity of mouse cell lines to apoptosis induced by chemotherapy, radiation, or activated cytotoxic T lymphocytes (CTLs). We find that, although cells expressing P210BCR-ABL by gene transfer are more resistant than their normal counterparts to apoptosis induced by chemotherapy or radiation, they are equally susceptible to apoptosis induced by alloreactive CTLs. These results show that CTLs overcome BCR-ABL-mediated resistance to apoptosis and, therefore, provide a biological correlation for the success of allogeneic bone marrow transplantation in chronic myelogenous leukemia.
Division of Bone Marrow Transplantation, Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8985.
E J
EJ
Fuchs
A
A
Bedi
R J
RJ
Jones
A D
AD
Hess
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D005047:Etoposide / Q000494:pharmacology; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D005047:Etoposide; D016044:Fusion Proteins, bcr-abl