Literature DB >> 25145343

NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report.

Fabiana Ostronoff1, Megan Othus2, Robert B Gerbing3, Michael R Loken4, Susana C Raimondi5, Betsy A Hirsch6, Beverly J Lange7, Stephen Petersdorf8, Jerald Radich1, Frederick R Appelbaum1, Alan S Gamis9, Todd A Alonzo10, Soheil Meshinchi11.   

Abstract

NUP98/NSD1 has recently been reported in association with poor outcome in acute myeloid leukemia (AML). Previous studies also observed a high overlap between NUP98/NSD1 and FLT3/ITD, raising the question as to whether the reported poor outcome is due to NUP98/NSD1 or caused by the co-occurrence of these 2 genetic lesions. We aimed to determine the prognostic significance of NUP98/NSD1 in the context of FLT3/ITD AML. A total of 1421 patients enrolled in 5 consecutive Children's Oncology Group/Children's Cancer Group and SWOG trials were evaluated. NUP98/NSD1 was found in 15% of FLT3/ITD and 7% of cytogenetically normal (CN)-AML. Those with dual FLT3/ITD and NUP98/NSD1 (82% of NUP98/NSD1 patients) had a complete remission rate of 27% vs 69% in FLT3/ITD without NUP98/NSD1 (P < .001). The corresponding 3-year overall survival was 31% vs 48% (P = .011), respectively. In CN-AML, patients with concomitant NUP98/NSD1 and FLT3/ITD had a worse outcome than those harboring NUP98/NSD1 only. In multivariate analysis, the dual NUP98/NSD1 and FLT3/ITD remained an independent predictor of poor outcome, and NUP98/NSD1 without FLT3/ITD lost its prognostic significance. Our study demonstrates that it is the interaction between NUP98/NSD1 and FLT3/ITD that determines the poor outcome of patients with NUP98/NSD1 disease.
© 2014 by The American Society of Hematology.

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Year:  2014        PMID： 25145343      PMCID： PMC4192751          DOI： 10.1182/blood-2014-04-570929

Source DB:  PubMed          Journal:  Blood        ISSN： 0006-4971            Impact factor:   22.113


  42 in total

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Journal:  Blood       Date:  2002-06-15       Impact factor: 22.113

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Journal:  Leukemia       Date:  2005-07       Impact factor: 11.528

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9.  Cryptic translocation t(5;11)(q35;p15.5) with involvement of the NSD1 and NUP98 genes without 5q deletion in childhood acute myeloid leukemia.

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Journal:  Blood       Date:  2002-08-01       Impact factor: 22.113
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