Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • T. Köhler - , Technische Universität Dresden (Autor:in)
  • R. Plettig - , Technische Universität Dresden (Autor:in)
  • W. Wetzstein - , Technische Universität Dresden (Autor:in)
  • M. Schmitz - , Institut für Immunologie (Autor:in)
  • M. Ritter - , Technische Universität Dresden (Autor:in)
  • B. Mohr - , Medizinische Klinik und Poliklinik I (Autor:in)
  • U. Schaekel - , Technische Universität Dresden (Autor:in)
  • G. Ehninger - , Technische Universität Dresden (Autor:in)
  • M. Bornhäuser - , Medizinische Klinik und Poliklinik I (Autor:in)

Abstract

We investigated the ability of both acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts to differentiate into dendritic cells (DC) in vitro. Cytokine-supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL (normal karyotype, n = 2; BCR/ABL, n = 3) were performed. Mononuclear cells out of peripheral blood or bone marrow containing between 60% and 90% leukemic blasts were cultured for eight days using different growth factor combinations. The highest yield of CD1a+/VCD14- cells could be obtained with stem cell factor, transforming growth factorβ, tumor necrosis factor-α, GM-CSF, and FLT-3-ligand. In the AML samples the median content of CD1a+/CD14- cells after eight days of culture was 3.5% (r = 0%-82%). In five informed patients CD1a+/CD14- cells were sorted by fluorescence-activated cell sorting or immunomagnetic separation. Cytogenetic and polymerase chain reaction analyses showed known primary chromosomal aberrations (monosomy 7 and inversion 16) in the sorted fraction, respectively. Dendritic cells (DC) could be generated out of leukemic blasts in 68% of AML patients. Leukemic DC showed no phagocytosis of latex beads, but stimulated allogeneic naive cord blood- derived T cells more efficiently than did uncultured blasts. In ALL patients the median percentage of CD1a+/CD14- cells was 1.2% (r = 0.7%3.8%) after culture. The sorted CD1+/CD14- fractions were BCR/ABL-negative when analyzed with fluorescence in situ hybridization, indicating their nonleukemic origin. Leukemic DC can be generated out of leukemic progenitors in patients with AML. These cells might become relevant for autologous and allogeneic immunotherapy in selected patients. BCR/ABL-positive lymphoblasts could not be transformed into cells with an early dendritic phenotype with the cytokines used in our experiments.

Details

OriginalspracheEnglisch
Seiten (von - bis)139-147
Seitenumfang9
FachzeitschriftStem cells
Jahrgang18
Ausgabenummer2
PublikationsstatusVeröffentlicht - 2000
Peer-Review-StatusJa

Externe IDs

PubMed 10742386

Schlagworte

Schlagwörter

  • Acute leukemia, Chromosomal aberrations, Dendritic cells, Immunotherapy