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Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 39-45
Complete Remission of t(11;17) Positive Acute Promyelocytic Leukemia
Induced by All-trans Retinoic Acid and Granulocyte
Colony-Stimulating Factor
J.H. Jansen,
M.C. de Ridder,
W.M.C. Geertsma,
C.A.J. Erpelinck,
K. van Lom,
E.M.E. Smit,
R. Slater,
B.A. vd Reijden,
G.E. de Greef,
P. Sonneveld, and
B. Löwenberg
From the Institute of Hematology, the Department of Clinical Genetics
and the Department of Cell Biology and Genetics, Erasmus University
Rotterdam, Rotterdam, The Netherlands.
The combined use of retinoic acid and chemotherapy has led to an
important improvement of cure rates in acute promyelocytic leukemia.
Retinoic acid forces terminal maturation of the malignant cells and
this application represents the first generally accepted differentiation-based therapy in leukemia. Unfortunately, similar approaches have failed in other types of hematological malignancies suggesting that the applicability is limited to this specific subgroup
of patients. This has been endorsed by the notorious lack of response
in acute promyelocytic leukemia bearing the variant t(11;17)
translocation. Based on the reported synergistic effects of retinoic
acid and the hematopoietic growth factor granulocyte colony-stimulating
factor (G-CSF), we studied maturation of t(11;17) positive leukemia
cells using several combinations of retinoic acid and growth factors.
In cultures with retinoic acid or G-CSF the leukemic cells did not
differentiate into mature granulocytes, but striking granulocytic
differentiation occurred with the combination of both agents. At
relapse, the patient was treated with retinoic acid and G-CSF before
reinduction chemotherapy. With retinoic acid and G-CSF treatment alone,
complete granulocytic maturation of the leukemic cells occurred in
vivo, followed by a complete cytogenetical and hematological remission.
Bone marrow and blood became negative in fluorescense in situ
hybridization analysis and semi-quantitative polymerase chain reaction
showed a profound reduction of promyelocytic leukemia zinc
finger-retinoic acid receptor- fusion transcripts. This shows that
t(11;17) positive leukemia cells are not intrinsically resistant to
retinoic acid, provided that the proper costimulus is administered.
These observations may encourage the investigation of combinations of
all-trans retinoic acid and hematopoietic growth factors in
other types of leukemia.
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