title: FLT3 mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia.
abstract: FMS-like tyrosine kinase III (FLT3) mutations occur in one-third of acute myeloid leukemia (AML) patients and predict poor outcome. The incidence and impact of FLT3 in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is unknown. We conducted a retrospective review to identify WHO MDS and CMML patients with FLT3 mutations at diagnosis. A total of 2,119 patients with MDS and 466 patients with CMML were evaluated at MD Anderson between 1997 and 2010. Of these, FLT3 mutation analysis was performed on 1,232 (58%) MDS and 302 (65%) CMML patients. FLT3 mutations were identified in 12 (0.95%) MDS patients: 9 (75%) had FLT3-ITD mutation and 3 had FLT3-tyrosine kinase domain (TKD) mutation. MDS patients with FLT3 mutations were younger (P = 0.02) and presented as RAEB (P = 0.03) more frequently. Median overall survival (OS) for FLT3-mutated MDS patients was 19.0 months versus 16.4 months for FLT3-nonmutated MDS patients (P = 0.08). FLT3 mutations were identified in 13 (4.3%) CMML patients: 8 had FLT3-ITD mutation and 5 had FLT3-TKD mutation. There were no significant differences in demographic and disease characteristics among CMML patients with and without FLT3 mutations. Median OS for FLT3-mutated CMML patients was 10.8 months versus 21.3 months for FLT3-nonmutated CMML patients (P = 0.12). FLT3 occurs in MDS and CMML at a lower frequency than AML and does not predict poor outcome.
authors.affiliation: Department of Leukemia and Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, USA.
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.forename: Paolo
authors.initials: P
authors.lastname: Strati
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.forename: Sa
authors.initials: S
authors.lastname: Wang
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Xiao
authors.initials: X
authors.lastname: Qin Dong
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D017434:Protein Structure, Tertiary; D012189:Retrospective Studies; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3