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 allogeneic bone marrow transplantation can be successfully treated with blood mononuclear cells from the original bone marrow donor. However, the antileukemic effect of this treatment is often accompanied by graft-versus-host disease (GVHD). Treatment with cytotoxic T-lymphocyte (CTL) lines or clones that are specifically generated against leukemic antigen-presenting cells from the patient, may separate antileukemic effects from GVHD. In this report we demonstrate that after culturing CD34-positive 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 morphology, phenotypic analysis, and their efficient capacity to stimulate allogeneic T lymphocytes. The expression of HLA and costimulatory molecules and the stimulatory capacity of the dendritic cell-enriched cell suspensions were optimal between days 7 and 10 after onset of the cultures. Fluorescence in situ hybridization revealed that all cultured dendritic cells contained the CML specific t(9;22) translocation. PCR analysis showed expression of the translocation specific bcr-abl mRNA. These leukemic dendritic cells may enhance the induction and proliferation of CTL lines and clones with more specificity for the leukemic cells.
Smit
W M
WM
Department of Hematology, Leiden University Hospital, The Netherlands.
Rijnbeek
M
M
van Bergen
C A
CA
de Paus
R A
RA
Vervenne
H A
HA
van de Keur
M
M
Willemze
R
R
Falkenburg
J H
JH
D018952:Antigens, CD34 / Q000032:analysis*; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000032:analysis; D014178:Translocation, Genetic
D018952:Antigens, CD34; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl