The identification and characterization of a novel human
differentiation-inhibiting protein that selectively blocks erythroid
differentiation
JP Durkin, JM Biquard, JF Whitfield, N Morardet, J Royer, P Macdonald, R Tremblay, JD Legal, R Doyonnas and JP Blanchet
Institute for Biological Sciences, National Research Council of Canada,
Ottawa, Ontario.
We have isolated a novel inhibitor of erythropoietic differentiation from
the plasma of a patient suffering from idiopathic pure red cell aplasia.
This differentiation-inhibiting protein (DIP) specifically blocked the
differentiation of human burst-forming unit-erythroid (BFU- E), but not
colony-forming unit-erythroid (CFU-E) cells. DIP also blocked the
maturation of murine BFU-E cells, but not CFU-E or CFU-
granulocyte-macrophage cells, and it inhibited the dimethyl sulfoxide
(DMSO)-induced differentiation of Friend murine erythroleukemia cells (FLC)
at levels between 10(-10) and 10(-12) mol/L. DIP activity was not
detectable in the plasma of normal, healthy subjects. Unlike other known
inhibitors of hematopoiesis, DIP appears to directly inhibit erythropoietic
differentiation, because it did not affect the proliferation of untreated
FLC and it effectively blocked FLC hemoglobinization without affecting the
ability of the blocked cells to proliferate. DIP blocked FLC
differentiation only when added to the culture medium within 1 hour of
inducing the cells with DMSO, suggesting that the protein inhibited an
early, but critical, DMSO- induced cellular process. DIP appears to be at
least partially responsible for the patient's anemia, and its unique
activity suggests a role in the early development of some erythroleukemias.
Volume 79,
Issue 5,
pp. 1161-1171,
03/01/1992
Copyright © 1992 by The American Society of Hematology
