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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2001-12-0368.
Submitted January 2, 2002
Accepted March 13, 2002
Complete remission through blast cell differentiation in PLZF/RAR -positive acute promyelocytic leukemia: In vitro and in vivo studies
Maria C Petti, Francesco Fazi, Massimo Gentile, Daniela Diverio, Paolo De Fabritiis, Stefania De Propris, Roberto Fiorini, Maria A Aloe Spiriti, Fabrizio Padula, Pier Giuseppe Pelicci, Clara Nervi, and Francesco Lo Coco*
Hematology, Regina Elena Cancer Institute, Roma, Italy
Histology and Medical Embriology, University of Rome, Roma, Italy
Cellular Biotechnology and Hematology, University of Rome, Roma, Italy
Experimental Oncology, European Institute of Oncology, Milano, Italy
* Corresponding author; email: lococo{at}bce.med.uniroma1.it.
Acute leukemia with the t(11;17) expressing the PLZF-RAR 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/RAR- APL who was treated at relapse with ATRA and 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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