Acute leukemia with the t(11;17) expressing the PLZF-RARalpha 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/RARalpha 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.
|Titolo:||Complete remission through blast cell differentiation in PLZF/RARalpha-positive acute promyelocytic leukemia: in vitro and in vivo studies|
|Parole Chiave:||Blast Crisis; Humans; Hydroxamic Acids; Cell Differentiation; Drug Resistance, Neoplasm; Enzyme Inhibitors; Neoplasm Proteins; Antineoplastic Combined Chemotherapy Protocols; Leukemia, Promyelocytic, Acute; Tretinoin; Middle Aged; Histone Deacetylase Inhibitors; Male; Oncogene Proteins, Fusion; Remission Induction|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||1-ago-2002|
|Digital Object Identifier (DOI):||10.1182/blood-2001-12-0368|
|Appare nelle tipologie:||01 - Articolo su periodico|