Complete remission through blast cell differentiation inPLZF/RARα-positive acute promyelocytic leukemia: in vitro and in vivo studies

MC Petti, F Fazi, M Gentile, D Diverio… - Blood, The Journal …, 2002 - ashpublications.org
MC Petti, F Fazi, M Gentile, D Diverio, P De Fabritiis, MS De Propris, R Fiorini, MAA Spiriti…
Blood, The Journal of the American Society of Hematology, 2002ashpublications.org
Acute leukemia with the t (11; 17) expressing the PLZF-RARα gene fusion is a rare variant of
acute promyelocytic leukemia (APL) that has been associated with poor clinical response to
all-trans retinoic acid (ATRA) treatment. However, some recent reports have put into
question the absolute refractoriness of this leukemia to ATRA. We describe here a patient
with PLZF/RARα APL who was treated at relapse with ATRA and low-dose hydroxyurea.
Complete hematologic remission was obtained through differentiation of leukemic blasts, as …
Abstract
Acute leukemia with the t(11;17) expressing the PLZF-RARαgene fusion is a rare variant of acute promyelocytic leukemia (APL) that has been associated with poor clinical response to all-trans retinoic acid (ATRA) treatment. However, some recent reports have put into question the absolute refractoriness of this leukemia to ATRA. We describe here a patient withPLZF/RARα APL who was treated at relapse with ATRA and low-dose hydroxyurea. Complete hematologic remission was obtained through differentiation of leukemic blasts, as proven by morphologic, immunophenophenotypic, and genetic studies carried out in sequential bone marrow samples. Moreover, in vitro studies indicated that blast differentiation was potentiated by the addition of the histone deacetylase inhibitor tricostatin A, but not of hydroxyurea, to ATRA. Our findings indicate that the maturation block may be overcome and terminal differentiation obtained in this leukemia subset and support the view that sensitivity/refractoriness of this form to ATRA should be revisited.
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