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Hematopoietic growth factor expression and ATRA sensitivity in acute
promyelocytic blast cells
C Dubois, MH Schlageter, A de Gentile, F Guidez, N Balitrand, ME Toubert, I Krawice, P Fenaux, S Castaigne and Y Najean
Laboratoire de Biologie Cellulaire Hematopoietique, Hopital Saint Louis,
Paris, France.
Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute
myeloid leukemias (AMLs) characterized by the presence of the t(15,17)
translocation and the resulting promyelocytic myeloid leukemia/retinoic
acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the
only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA)
differentiating effect. In vivo ATRA alone achieves complete remission in
most APL patients. However, failure or partial responses are observed and
the molecular basis of the absence of ATRA response in these patients has
not been determined. To gain insights in the cell growth and
differentiation of APL cells, expression of hematopoietic growth factors
(HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1
beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte
colony-stimulating factor [G-CSF], granulocyte- macrophage
colony-stimulating factor [GM-CSF], and IL-3) was studied in 16 APL
samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not
G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA
therapy. The four remaining patients (either TNF alpha negative or G-CSF,
GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In
all cases, in vivo response to ATRA therapy was correlated to the in vitro
differentiation effect of all- trans retinoic acid 10(-6) mol/L. Thus, ATRA
differentiation induction was strongly correlated to the HGF expression (P
< .0001). These results suggest that the presence or absence of HGF's
expression by APL cells may contribute to the therapeutic effect of ATRA in
this disease.
Volume 83,
Issue 11,
pp. 3264-3270,
06/01/1994
Copyright © 1994 by The American Society of Hematology
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