BACKGROUND: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. METHODS: We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. RESULTS: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p<0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.
BACKGROUND: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. METHODS: We analyzed 102 MDSpatients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. RESULTS: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p<0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.
Authors: Matthew J Walter; Dong Shen; Li Ding; Jin Shao; Daniel C Koboldt; Ken Chen; David E Larson; Michael D McLellan; David Dooling; Rachel Abbott; Robert Fulton; Vincent Magrini; Heather Schmidt; Joelle Kalicki-Veizer; Michelle O'Laughlin; Xian Fan; Marcus Grillot; Sarah Witowski; Sharon Heath; John L Frater; William Eades; Michael Tomasson; Peter Westervelt; John F DiPersio; Daniel C Link; Elaine R Mardis; Timothy J Ley; Richard K Wilson; Timothy A Graubert Journal: N Engl J Med Date: 2012-03-14 Impact factor: 91.245
Authors: F Dicker; C Haferlach; J Sundermann; N Wendland; T Weiss; W Kern; T Haferlach; S Schnittger Journal: Leukemia Date: 2010-06-03 Impact factor: 11.528
Authors: Rafael Bejar; Kristen Stevenson; Omar Abdel-Wahab; Naomi Galili; Björn Nilsson; Guillermo Garcia-Manero; Hagop Kantarjian; Azra Raza; Ross L Levine; Donna Neuberg; Benjamin L Ebert Journal: N Engl J Med Date: 2011-06-30 Impact factor: 91.245
Authors: Amy E DeZern; Anthony Sung; Sharon Kim; B Douglas Smith; Judith E Karp; Steven D Gore; Richard J Jones; Ephraim Fuchs; Leo Luznik; Michael McDevitt; Mark Levis Journal: Biol Blood Marrow Transplant Date: 2011-02-13 Impact factor: 5.742
Authors: Li Ding; Timothy J Ley; David E Larson; Christopher A Miller; Daniel C Koboldt; John S Welch; Julie K Ritchey; Margaret A Young; Tamara Lamprecht; Michael D McLellan; Joshua F McMichael; John W Wallis; Charles Lu; Dong Shen; Christopher C Harris; David J Dooling; Robert S Fulton; Lucinda L Fulton; Ken Chen; Heather Schmidt; Joelle Kalicki-Veizer; Vincent J Magrini; Lisa Cook; Sean D McGrath; Tammi L Vickery; Michael C Wendl; Sharon Heath; Mark A Watson; Daniel C Link; Michael H Tomasson; William D Shannon; Jacqueline E Payton; Shashikant Kulkarni; Peter Westervelt; Matthew J Walter; Timothy A Graubert; Elaine R Mardis; Richard K Wilson; John F DiPersio Journal: Nature Date: 2012-01-11 Impact factor: 49.962