GENERATION OF DENDRITIC CELLS EXPRESSING BCR-ABL FROM CD34-POSITIVE CHRONIC MYELOID-LEUKEMIA PRECURSOR CELLS

Patients with a relapse of chronic myeloid leukemia (CML) after alloge neic bone marrow transplantation can be successfully created with bloo d mononuclear cells from the original bone marrow donor. However, the antileukemic effect of this treatment is often accompanied by graft-ve rsus-host disease (GVHD). Treatment with cytotoxic T-lymphocyte (CTL) lines or clones that are specifically generated against leukemic antig en-presenting cells from che patient, may separate antileukemic effect s from GVHD. In this report we demonstrate that after culturing CD34-p ositive cells purified from bone marrow of patients with chronic phase CML in medium containing human serum, GM-CSF, TNF alpha, and IL-4 up to 28% of the cultured cells were dendritic cells, characterized by mo rphology, phenotypic analysis, and their efficient capacity to stimula te allogeneic T lymphocytes. The expression of HLA and costimulatory m olecules and the stimulatory capacity of the dendritic cell-enriched c ell suspensions were optimal between days 7 and 10 after onset of the cultures. Fluorescence in situ hybridization revealed that all culture d dendritic cells contained the Chit specific t(9;22) translocation. P CR analysis showed expression of the translocation specific bcr-abl mR NA. These leukemic dendritic cells may enhance the induction and proli feration of CTL lines and clones with more specificity for the leukemi c cells. (C) American Society for Histocompatibility and Immunogenetic s, 1997.