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Cytotoxic T Cells Overcome BCR-ABL-mediated Resistance to Apoptosis¹

Division of Bone Marrow Transplantation, The Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8985

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 P210^BCR-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 P210^BCR-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.

¹ Supported by Grant CA-15396 from the National Cancer Institute. R. J. J. is a Leukemia Society of America Scholar.

² To whom requests for reprints should be addressed, at Division of Bone Marrow Transplantation, The Johns Hopkins Oncology Center, 600 North Wolfe Street, Baltimore, MD 21287-8985.

Received 11/ 4/94. Accepted 12/16/94.

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