PMID- 10477734 OWN - NLM STAT- MEDLINE DCOM- 19991012 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 94 IP - 6 DP - 1999 Sep 15 TI - CD34(+) acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. PG - 2048-55 AB - CD34(+) hematopoietic stem cells from normal individuals and from patients with chronic myelogenous leukemia can be induced to differentiate into dendritic cells (DC). The aim of the current study was to determine whether acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cells could 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 (TNFalpha), and interleukin-4 (IL-4). After 3 weeks of culture, 35% of the AML-M2 cells showed DC morphology and phenotype. The DC phenotype was defined as upmodulation of the costimulatory molecules CD80 and CD86 and the expression of CD1a or CD83. The leukemic nature of the DC was validated by detection of chromosome 7 monosomy in sorted DC populations by fluorescence in situ hybridization (FISH). CD34(+) leukemic cells from 2 B-ALL patients with the Philadelphia chromosome were similarly cultured, but in the presence of CD40-ligand and 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 detection of the bcr-abl fusion gene in sorted DC populations by FISH. In functional studies, the leukemic DC were highly superior to the parental leukemic 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. FAU - Cignetti, A AU - Cignetti A AD - Corixa Corp, Seattle, WA; the Fred Hutchinson Cancer Research Center, Seattle, WA; the Divisione Ospedaliera di Ematologia, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy. FAU - Bryant, E AU - Bryant E FAU - Allione, B AU - Allione B FAU - Vitale, A AU - Vitale A FAU - Foa, R AU - Foa R FAU - Cheever, M A AU - Cheever MA LA - eng GR - 5 R37 CA30558/CA/NCI NIH HHS/United States GR - CA81029/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (Antigens, CD34) SB - IM MH - Antigens, CD/blood MH - Antigens, CD34/blood MH - Cell Differentiation MH - Cells, Cultured MH - Chromosomes, Human, Pair 7 MH - Dendritic Cells/immunology/pathology MH - Flow Cytometry MH - Genotype MH - Hematopoietic Stem Cells/*immunology/pathology MH - Humans MH - Immunophenotyping MH - Leukemia, Myeloid, Acute/*blood/genetics/immunology/pathology MH - Monosomy MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*blood/immunology/pathology MH - Time Factors EDAT- 1999/09/09 00:00 MHDA- 1999/09/09 00:01 CRDT- 1999/09/09 00:00 PHST- 1999/09/09 00:00 [pubmed] PHST- 1999/09/09 00:01 [medline] PHST- 1999/09/09 00:00 [entrez] AID - S0006-4971(20)48912-8 [pii] PST - ppublish SO - Blood. 1999 Sep 15;94(6):2048-55.