RESUMEN
BACKGROUND: Prognostication of AML patients depends on association of genetic and epigenetic abnormalities. We aimed to evaluate the frequency and prognostic significance of Additional Sex comb's Like1 (ASXL1), Isocitrate Dehydrogenase (IDH) and Casitas B- lineage Lymphoma (CBL) mutations in AML assessing their association with different cytogenetic risk category. METHODS: We used High Resolution Melting (HRM) technology that detects small differences in PCR amplified sequences by direct melting using EvaGreen saturating dye to analyze epigenetic mutations in 70 denovo AML patients. RESULTS: Median age of AML patients was 39.5 years (18-75). ASXL1, IDH and CBL mutations were detected in 14 (20%), 10 (14%) and 5 (7%) patients, respectively. Mean age of ASXL1 and IDH mutants vs. wild type was 35.9±14.6 years and 42.9±14.4 years (p=0.114) and 46.7±15.2 years vs. 40.6±14.5 years (p=0.290), respectively. AML cytogenetic risk groups included low (25/70, 36%), intermediate (33/70, 47%) and high-risk (12/70, 17%). Nine/14 (64%) ASXL1 and 8/10 (80%) IDH mutants were classified as intermediate risk and 9 ASXL1 positive (64%) were adolescent and young adults (AYA). Overall survival (OS) of mutant ASXL1 vs. wild type was 1.1 years (95% CI 0.83-1.4) vs. 1.9 years (95% CI 0.71-7.51), respectively (p=0.056). OS of mutant IDH vs. wild type was 1.25 years (95% CI 0.85-1.6) vs. 1.8 years (95% CI 1.2-6.7), respectively (p=0.020). In intermediate risk cytogenetic group, ASXL1 and IDH mutants had shorter OS than wild type; 1.1 years (95% CI 0.97-1.2) vs. 2.1 years (95% CI 0.14-10.8) (p=0.002) and 1.8 years (95% CI 0.69-3.15) vs. 2.3 years (95% CI 1.1-5.5) (p=0.05), respectively. CONCLUSION: ASXL1 and IDH mutations occur at a high incidence among young Egyptian AML patients with intermediate risk cytogenetics and confer a poorer outcome. Integration of mutations into risk profiling may predict outcome and impact therapeutic approach of young AML patient with uncertain prognosis.
Asunto(s)
Isocitrato Deshidrogenasa , Leucemia Mieloide Aguda , Proteínas Represoras , Adolescente , Adulto , Anciano , Egipto/epidemiología , Humanos , Isocitrato Deshidrogenasa/genética , Persona de Mediana Edad , Mutación , Proteínas Represoras/genética , Adulto JovenRESUMEN
OBJECTIVE: IDH mutations diversely affect the prognosis of cyogenetically normal acute myeloid leukemia (CN-AML) adult patients. The aim of this study is to assess the frequency of IDH mutations and to evaluate its role in AML prognosis. METHODS: We have analyzed IDH1 and 2 mutations using High Resolution Melting curve analysis (HRM) in 70 denovo AML patients. RESULTS: The median age of AML patients is 40 years (16-75). Incidence of IDH mutations is 10/70 (14.3%); 2 (2.9%) IDH1 mutant and 8 (11.4%) IDH2 mutant. Median PB blasts of mutant IDH patients was 67.5% (25-96) vs. 44% (0-98) for wild type (p=0.065). Eight/10 (80%) mutant IDH patients had B.M blasts ≥50% vs. 2/10 (20%) <50% (p<0.001) and were classified as intermediate risk cytogenetics (p=0.020) with wild FLT3-ITD (p=0.001). Ten/10 (100%) mutant IDH patients showed wild NPM1 (p=0.049). Median OS of mutant IDH in the intermediate risk cytogenetics was 1.8 years (0.7-3.1) vs. 3.1 years (1.1-5.5) for wild IDH (p=0.05). CONCLUSION: IDH mutation is mainly associated with intermediate risk AML and when integrated in this specific subgroup displays a lower survival and can be considered an additional integrated molecular risk marker for AML prognosis.
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Asunto(s)
Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/genética , Mutación , Adolescente , Adulto , Anciano , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Nucleofosmina , Factores de Riesgo , Adulto JovenRESUMEN
JAK2, CALR, MPL and triple-negative mutational status has a direct impact on symptom severity and disease burden assessed by MPN10 score in myeloproliferative neoplasms (MPNs). Among 93 patients; median MPN10 score was 48 (5-76) in JAK2 mutants versus 25 (4-80) in JAK2 negative (p < .001); 22.5 (4-65) in CALR mutants versus 35 (5-80) in CALR negative (p < .050) and 21 (10-48) in triple negative versus 40 (4-80) in JAK2/CALR/MPL mutants (p < .001). At three years, progression free and overall survival of JAK2-positive versus JAK2-negative patients were 62% versus 100% (p < .001); 85% versus 100% (p = .011) and were 100% versus 78% (p = .067); 100% versus 92% (p = .197) in CALR-positive versus CALR-negative patients and 100% versus 75% (p = .004); 100% versus 90% (p = .015) in triple negative versus mutant patients, respectively. MPN10 score in association with driver gene mutations can be used as a predictor of survival in MPN patients.
