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Diamond-blackfan anemia: in vitro response of erythroid progenitors to the
ligand for c-kit
JL Abkowitz, KM Sabo, B Nakamoto, CA Blau, FH Martin, KM Zsebo and T Papayannopoulou
Department of Medicine, University of Washington, Seattle 98195.
To provide insights into the pathogenesis of Diamond-Blackfan anemia, we
examined the in vitro response of erythroid progenitors to the recently
isolated ligand for c-kit (stem cell factor, SCF). For these studies,
marrow or blood mononuclear cells from 10 Diamond-Blackfan patients were
cultured with erythropoietin (Ep), Ep and interleukin-3, Ep and
granulocyte-macrophage colony-stimulating factor, or Ep and lymphocyte
conditioned media (LCM). These combinations were tested in the presence or
absence of SCF. The mean number of cells per erythroid burst increased 5 to
50-fold in cultures containing SCF. Furthermore, many additional erythroid
bursts were seen (mean increment 3.2 x baseline values). Although
burst-forming unit-erythroid (BFU-E) from all patients responded, there
were differences among individuals in the sensitivity of their BFU-E to
SCF. In six patients and all control studies, plateau frequencies of
erythroid bursts were achieved with less than or equal to 10 ng/mL SCF,
whereas in studies from the other four patients, over 50 ng/mL SCF was
required. These data invite speculation that the c-kit receptor/ligand axis
is involved in the pathogenesis of Diamond-Blackfan anemia. More
importantly and regardless of whether the observed patterns of response
reflect the primary defect or an epiphenomenon, our data strongly support a
therapeutic trial of SCF in patients with Diamond-Blackfan anemia.
Volume 78,
Issue 9,
pp. 2198-2202,
11/01/1991
Copyright © 1991 by The American Society of Hematology
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