title: Hypoxia-inducible factor-1α protein expression is associated with poor survival in normal karyotype adult acute myeloid leukemia.
abstract: We examined the predictive impact of HIF-1α protein expression on clinical outcome of 84 normal karyotype acute myeloid leukemia (NK-AML) patients (median age 66.5 years) at our institute. Thirty percent of NK-AML cells expressed cytoplasmic HIF-1α. In univariate analysis, low HIF-1α (≤ 5%, n = 66) was associated with improved event-free survival (p = 0.0453, HR = 0.22). Multivariate analysis incorporating age, complete remission, FLT3-ITD mutation, and marrow blast percentage demonstrated that HIF-1α was independently associated with poorer overall and event-free survival. HIF-1α expression correlated with VEGF-C but not VEGF-A, marrow angiogenesis, FLT3 ITD or NPM1 mutations. These results support HIF-1α as an outcome marker for NK-AML.
authors.affiliation: Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: George
authors.initials: G
authors.lastname: Deeb
authors.forename: Mary M
authors.initials: MM
authors.lastname: Vaughan
authors.forename: Ian
authors.initials: I
authors.lastname: McInnis
authors.forename: Laurie Ann
authors.initials: LA
authors.lastname: Ford
authors.forename: Sheila N J
authors.initials: SN
authors.lastname: Sait
authors.forename: Petr
authors.initials: P
authors.lastname: Starostik
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Terry
authors.initials: T
authors.lastname: Mashtare
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000716967:NPM1 protein, human; D000090243:Nucleophosmin