CD34(+) acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells

CD34(+) hematopoietic stem cells from normal individuals and from patients with chronic myelogenous leukemia can be induced to differentiate into dend ritic cells (DC). The aim of the current study was to determine whether acu te myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cells coul d be induced to differentiate into DC. CD34(+) AML-M2 cells with chromosome 7 monosomy were cultured in the presence of granulocyte-macrophage colony- stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF alpha), and i nterleukin-4 (IL-4), After 3 weeks of culture, 35% of the AML-M2 cells show ed DC morphology and phenotype. The DC phenotype was defined as upmodulatio n of the costimulatory molecules CD80 and CD86 and the expression of CD1a o r CD83. The leukemic nature of the DC was validated by detection of chromos ome 7 monosomy in sorted DC populations by fluorescence in situ hybridizati on (FISH), CD34(+) leukemic cells from 2 B-ALL patients with the Philadelph ia chromosome were similarly cultured, but in the presence of CD40-ligand a nd IL-4, After 4 days of culture, more than 58% of the ALL cells showed DC morphology and phenotype. The leukemic nature of the DC was validated by de tection of the bcr-abl fusion gene in sorted DC populations by FISH. In fun ctional studies, the leukemic DC were highly superior to the parental leuke mic blasts for inducing allogeneic T-cell responses, Thus, CD34(+) AML and ALL cells can be induced to differentiate into leukemic DC with morphologic , phenotypic, and functional similarities to normal DC. (C) 1999 by The Ame rican Society of Hematology.