RESUMO
Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We also found an association between VEGFC expression and the patient cytogenetic risk group, with those with a worse prognosis having higher VEGFC expression levels. No correlation was observed between VEGFC expression and survival or complete remission. VEGFC expression strongly correlated with expression of the VEGF receptors FLT1, KDR, and NRP1. Thus, in this series, VEGFC expression was increased in AML-MRC and in subgroups with a poorer prognosis, but has no impact on survival.
Assuntos
Biomarcadores Tumorais/metabolismo , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/patologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Medula Óssea/patologia , Aberrações Cromossômicas , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Neuropilina-1/metabolismo , Prognóstico , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
OBJECTIVES: The prognostic impact of immunophenotypic markers in acute myeloid leukemia (AML) is controversial. METHODS: We retrospectively analyzed the value of CD34, CD117, CD7, and CD123 expression in a consecutive series of 592 adult patients with de novo AML. RESULTS: CD34+ measured as a percentage (≥2.88%) and CD34 mean fluorescence intensity (MFI) (≥146.79, arbitrary units [AU]) expression had a prognostic impact in terms of overall survival (OS; P = .005, P = .003), leukemia-free survival (LFS; P = .011, P < .001), and cumulative incidence of relapse (CIR; P = .014, P =. 001). The percentage of CD117+ cells (61.29%) was associated with shorter LFS (P =. 043), and CD117 MFI (≥284.01 AU) was associated with a shorter OS (P =. 033) and LFS (P =. 028). In the multivariate analysis, high CD34 MFI retained the independent value as predictor of LFS and CIR (P =. 012; hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.11-2.28 and P =. 045; HR, 1.58; 95% CI, 1.01-2.46). CONCLUSIONS: CD34 positivity threshold with prognostic relevance is low (3% positive cells). Immunophenotypic findings in AML probably could only be fully exploited after a complex analysis that takes into account unconventional thresholds and the MFI.