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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 2048-2055
CD34+ Acute Myeloid and Lymphoid Leukemic Blasts Can
Be Induced to Differentiate Into Dendritic Cells
A. Cignetti,
E. Bryant,
B. Allione,
A. Vitale,
R. Foa, and
M.A. Cheever
From Corixa Corp, Seattle, WA; the Fred Hutchinson Cancer Research
Center, Seattle, WA; the Divisione Ospedaliera di Ematologia, Azienda
Ospedaliera S. Giovanni Battista, Torino, Italy; the Dipartimento di
Biotecnologie Cellulari ed Ematologia, University "La Sapienza,"
Rome, Italy; and the Dipartimento di Scienze Biomediche ed Oncologia
Umana, University of Torino, Torino, Italy.
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  (TNF),
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.
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