CYTOTOXIC T-CELLS OVERCOME BCR-ABL MEDIATED RESISTANCE TO APOPTOSIS

Chronic myeloid leukemia is a disease marked by expanded clonal hemato poiesis; it is incurable by chemotherapy or radiation but is cured in a majority of patients receiving bone marrow transplantation from noni dentical sibling donors, an outcome generally attributed to a T cell-m ediated graft-versus-leukemia effect. In this report, we examine the e ffect of the P210(BCR-ABL) fusion protein of the BCR-ABL oncogene, the molecular hallmark of chronic myelogenous leukemia, on the sensitivit y of mouse cell lines to apoptosis induced by chemotherapy, radiation, or activated cytotoxic T lymphocytes (CTLs). We find that, although c ells expressing p210(BCR-ABL) by gene transfer are more resistant than their normal counterparts to apoptosis induced by chemotherapy or rad iation, they are equally susceptible to apoptosis induced by alloreact ive CTLs. These results show that CTLs overcome BCR-ABL-mediated resis tance to apoptosis and, therefore, provide a biological correlation fo r the success of allogeneic bone marrow transplantation in chronic mye logenous leukemia.