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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2001-12-0368.
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Blood, 1 August 2002, Vol. 100, No. 3, pp. 1065-1067
BRIEF REPORT
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,
M. Stefania De
Propris,
Roberto Fiorini,
Maria A. Aloe Spiriti,
Fabrizio Padula,
Pier Giuseppe Pelicci,
Clara Nervi, and
Francesco Lo Coco
From the Hematology section, Regina Elena Cancer
Institute, Department of Cellular Biotechnology and Hematology section,
Department of Histology and Medical Embriology, University "La
Sapienza," Rome, Italy; the Department of Experimental Oncology,
European Institute of Oncology, Milan, Italy.
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
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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