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

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.

• Authors: Fabiana Ostronoff, Megan Othus, Robert B Gerbing, Michael R Loken, Susana C Raimondi, Betsy A Hirsch, Beverly J Lange, Stephen Petersdorf, Jerald Radich, Frederick R Appelbaum, Alan S Gamis, Todd A Alonzo, Soheil Meshinchi
• Journal: Blood (Blood) Vol. 124 Issue 15 Pg. 2400-7 (Oct 09 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 25145343 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• NUP98-NSD1 protein, human
• Oncogene Proteins, Fusion
• FLT3 protein, human
• fms-Like Tyrosine Kinase 3

Topics

• Adolescent
• Age Distribution
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Infant, Newborn
• Kaplan-Meier Estimate
• Leukemia, Myeloid, Acute (metabolism, therapy)
• Male
• Multivariate Analysis
• Neoplasm, Residual (pathology)
• Oncogene Proteins, Fusion (metabolism)
• Regression Analysis
• Remission Induction
• Treatment Failure
• Young Adult
• fms-Like Tyrosine Kinase 3 (metabolism)