Literature DB >> 12522450

Variable prognostic value of FLT3 internal tandem duplications in patients with de novo AML and a normal karyotype, t(15;17), t(8;21) or inv(16).

Birgit Kainz1, Daniel Heintel, Rodrig Marculescu, Ilse Schwarzinger, Wolfgang Sperr, Trang Le, Ansgar Weltermann, Christa Fonatsch, Oskar A Haas, Christine Mannhalter, Klaus Lechner, Ulrich Jaeger.   

Abstract

INTRODUCTION: Internal tandem duplication of the FLT3 gene (FLT3/ITD) has been linked to poor outcome in acute myeloid leukemia (AML). However, the prognostic value of FLT3/ITD in various cytogenetic risk groups is still a matter of debate. The aim of this study was to evaluate the prognostic significance in patients with de novo AML and a normal karyotype or a t(15;17), t(8;21) or inv(16) (good risk group). PATIENTS AND METHODS: Diagnostic samples of 100 patients were investigated by single-step PCR of exons 11 and 12 of the FLT3 gene in a single center retrospective analysis. Subgroups included 53 patients with normal karyotype, 21 patients with t(15;17), 9 patients with t(8;21) and 17 patients with inv(16).
RESULTS: FLT3/ITD was found in 26 out of 100 patients: 30% of patients with a normal karyotype and 38% of t(15;17) patients tested positive. The complete remission (CR) rates for the ITD(+) or ITD(-) groups were 50 vs 76% in normal karyotypes, and 100 vs 53% in t(15;17) patients, while the relapse rates were 75 vs 25% in normal karyotypes and 50 vs 42% in t(15;17) patients. Overall survival (OS) and disease free survival (DFS) at 5 years were significantly different in patients with normal cytogenetics: ITD(+) vs ITD(-): OS 6 vs 28% (P<0.003); DFS 13 vs 41% (P<0.02) Interestingly, FLT3/ITD had no significant effect on the outcome of t(15;17) patients: ITD(+) vs ITD(-): OS 85 vs 53% (P=0.056), DFS 45 vs 60% (P=0.6) at 50 months.
CONCLUSIONS: These data suggest a high prognostic value of FLT3/ITD in patients with normal cytogenetics. However, we find no evidence that FLT3/ITD is a predictive marker for patients with t(15;17).

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Year:  2002        PMID: 12522450     DOI: 10.1038/sj.thj.6200196

Source DB:  PubMed          Journal:  Hematol J        ISSN: 1466-4860


  22 in total

Review 1.  Clinical significance of FLT3 in leukemia.

Authors:  Hitoshi Kiyoi; Masamitsu Yanada; Kazutaka Ozekia
Journal:  Int J Hematol       Date:  2005-08       Impact factor: 2.490

Review 2.  FLT3 inhibitors in the treatment of acute myeloid leukemia: the start of an era?

Authors:  Naveen Pemmaraju; Hagop Kantarjian; Farhad Ravandi; Jorge Cortes
Journal:  Cancer       Date:  2011-02-11       Impact factor: 6.860

3.  Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with t(15;17)/PML-RARA.

Authors:  Susanne Schnittger; Ulrike Bacher; Claudia Haferlach; Wolfgang Kern; Tamara Alpermann; Torsten Haferlach
Journal:  Haematologica       Date:  2011-08-22       Impact factor: 9.941

4.  FLT3-ITD impedes retinoic acid, but not arsenic, responses in murine acute promyelocytic leukemias.

Authors:  Cécile Esnault; Ramy Rahmé; Kim L Rice; Caroline Berthier; Coline Gaillard; Samuel Quentin; Anne-Lise Maubert; Scott Kogan; Hugues de Thé
Journal:  Blood       Date:  2019-01-23       Impact factor: 22.113

5.  Intensive consolidation with G-CSF support: Tolerability, safety, reduced hospitalization, and efficacy in acute myeloid leukemia patients ≥60 years.

Authors:  Wolfgang R Sperr; Susanne Herndlhofer; Karoline Gleixner; Michael Girschikofsky; Ansgar Weltermann; Sigrid Machherndl-Spandl; Thamer Sliwa; Rainer Poehnl; Veronika Buxhofer-Ausch; Karin Strecker; Gregor Hoermann; Paul Knoebl; Ulrich Jaeger; Klaus Geissler; Michael Kundi; Peter Valent
Journal:  Am J Hematol       Date:  2017-08-17       Impact factor: 10.047

6.  Genetic abnormalities in acute myelogenous leukemia with normal cytogenetics.

Authors:  David Wald; Johanna M Vermaat; Gil Peleg; William Tse
Journal:  Curr Hematol Malig Rep       Date:  2008-04       Impact factor: 3.952

Review 7.  Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?

Authors:  Krzysztof Mrózek; Guido Marcucci; Peter Paschka; Susan P Whitman; Clara D Bloomfield
Journal:  Blood       Date:  2006-09-07       Impact factor: 22.113

8.  Clinical outcome of patients with acute promyelocytic leukemia and FLT3 mutations.

Authors:  Harshabad Singh; Lillian Werner; Daniel Deangelo; Karen Ballen; Philip Amrein; Martha Wadleigh; Donna Neuberg; Edward Fox; Richard Stone; Eyal Attar
Journal:  Am J Hematol       Date:  2010-12       Impact factor: 10.047

Review 9.  Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics.

Authors:  Tara K Gregory; David Wald; Yichu Chen; Johanna M Vermaat; Yin Xiong; William Tse
Journal:  J Hematol Oncol       Date:  2009-06-02       Impact factor: 17.388

10.  Possible involvement of RasGRP4 in leukemogenesis.

Authors:  Naoko Watanabe-Okochi; Toshihiko Oki; Yukiko Komeno; Naoko Kato; Koichiro Yuji; Ryoichi Ono; Yuka Harada; Hironori Harada; Yasuhide Hayashi; Hideaki Nakajima; Tetsuya Nosaka; Jiro Kitaura; Toshio Kitamura
Journal:  Int J Hematol       Date:  2009-04-07       Impact factor: 2.490

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