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

Autor:	Ostronoff F; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA; University of Washington, Seattle, WA;, Othus M; Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA; SWOG Statistical Center, Seattle, WA;, Gerbing RB; Children's Oncology Group, Arcadia, CA;, Loken MR; Hematologics, Inc., Seattle, WA;, Raimondi SC; St. Jude Children's Research Hospital, Pathology Division, Memphis, TN;, Hirsch BA; University of Minnesota Medical Center-Fairview, Minneapolis, MN;, Lange BJ; Children's Hospital of Philadelphia, Department of Pediatrics, Division of Oncology, Philadelphia, PA;, Petersdorf S; Seattle Genetics, Inc., Seattle, WA;, Radich J; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA; University of Washington, Seattle, WA;, Appelbaum FR; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA; University of Washington, Seattle, WA;, Gamis AS; Children's Oncology Group, Arcadia, CA; Children's Mercy Hospitals and Clinics, Kansas City, MO; and., Alonzo TA; Children's Oncology Group, Arcadia, CA; University of Southern California, Los Angeles, CA., Meshinchi S; Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA; Children's Oncology Group, Arcadia, CA;
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2014 Oct 09; Vol. 124 (15), pp. 2400-7. Date of Electronic Publication: 2014 Aug 21.
DOI:	10.1182/blood-2014-04-570929
Abstrakt:	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.)
Databáze:	MEDLINE
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