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

Author:

Petti Maria C.1,Fazi Francesco1,Gentile Massimo1,Diverio Daniela1,De Fabritiis Paolo1,De Propris M. Stefania1,Fiorini Roberto1,Spiriti Maria A. Aloe1,Padula Fabrizio1,Pelicci Pier Giuseppe1,Nervi Clara1,Lo Coco Francesco1

Affiliation:

1. 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.

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference13 articles.

1. Fusion between a novel Kruppel-like zinc finger gene and retinoic acid receptor-α locus due to a variant t(11;17) translocation associated with acute promyelocytic leukemia.;Chen;EMBO J.,1993

2. Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17).;Licht;Blood.,1995

3. A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements.;Sainty;Blood.,2000

4. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party.;Grimwade;Blood.,2000

5. Hypergranular promyelocytic leukemia: correlation between morphology and chromosomal translocations including t(15;17) and t(11;17).;Bennett;Leukemia.,2000

Cited by 59 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3