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Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes.

Devillier R, Mansat-De Mas V, Gelsi-Boyer V, Demur C, Murati A, Corre J, Prebet T, Bertoli S, Brecqueville M, Arnoulet C, Recher C, Vey N, Mozziconacci MJ, Delabesse E, Birnbaum D - Oncotarget (2015)

Bottom Line: ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030).In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS.We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Hematology Department, Institut Paoli Calmettes, Marseille, France.

ABSTRACT
Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroups based on mutations of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in complex karyotype AML (26/28) and predicted poor outcome within unfavorable cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis. This could be useful for future diagnostic and prognostic classifications.

No MeSH data available.


Related in: MedlinePlus

Overall survival according to the presence of ASXL1 or TP53 mutation
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Figure 3: Overall survival according to the presence of ASXL1 or TP53 mutation

Mentions: Using only the mutational status of ASXL1 and TP53 to stratify patient outcome, we found that patients who presented with either ASXL1 or TP53 mutation had worse 2-year OS (15%) than those with both ASXL1 and TP53 wild type (29%, p = 0.005, Table 3, Figure 3). In multivariate analysis including age, WBC and cytogenetics, the presence of either ASXL1 or TP53 mutation remained the only independent predictive factor associated with both lower CR rate (HR = 0.29, 95%CI = [0.09-0.89], p = 0.031) and shorter OS (HR = 2.53, 95%CI = [1.40-4.60], p = 0.002).


Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes.

Devillier R, Mansat-De Mas V, Gelsi-Boyer V, Demur C, Murati A, Corre J, Prebet T, Bertoli S, Brecqueville M, Arnoulet C, Recher C, Vey N, Mozziconacci MJ, Delabesse E, Birnbaum D - Oncotarget (2015)

Overall survival according to the presence of ASXL1 or TP53 mutation
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480760&req=5

Figure 3: Overall survival according to the presence of ASXL1 or TP53 mutation
Mentions: Using only the mutational status of ASXL1 and TP53 to stratify patient outcome, we found that patients who presented with either ASXL1 or TP53 mutation had worse 2-year OS (15%) than those with both ASXL1 and TP53 wild type (29%, p = 0.005, Table 3, Figure 3). In multivariate analysis including age, WBC and cytogenetics, the presence of either ASXL1 or TP53 mutation remained the only independent predictive factor associated with both lower CR rate (HR = 0.29, 95%CI = [0.09-0.89], p = 0.031) and shorter OS (HR = 2.53, 95%CI = [1.40-4.60], p = 0.002).

Bottom Line: ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030).In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS.We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Hematology Department, Institut Paoli Calmettes, Marseille, France.

ABSTRACT
Acute myeloid leukemias (AML) with myelodysplasia-related changes (AML-MRC) are defined by the presence of multilineage dysplasia (MLD), and/or myelodysplastic syndrome (MDS)-related cytogenetics, and/or previous MDS. The goal of this study was to identify distinct biological and prognostic subgroups based on mutations of ASXL1, RUNX1, DNMT3A, NPM1, FLT3 and TP53 in 125 AML-MRC patients according to the presence of MLD, cytogenetics and outcome. ASXL1 mutations (n=26, 21%) were associated with a higher proportion of marrow dysgranulopoiesis (mutant vs. wild-type: 75% vs. 55%, p=0.030) and were mostly found in intermediate cytogenetic AML (23/26) in which they predicted inferior 2-year overall survival (OS, mutant vs. wild-type: 14% vs. 37%, p=0.030). TP53 mutations (n=28, 22%) were mostly found in complex karyotype AML (26/28) and predicted poor outcome within unfavorable cytogenetic risk AML (mutant vs. wild-type: 9% vs. 40%, p=0.040). In multivariate analysis, the presence of either ASXL1 or TP53 mutation was the only independent factor associated with shorter OS (HR, 95%CI: 2.53, 1.40-4.60, p=0.002) while MLD, MDS-related cytogenetics and previous MDS history did not influence OS. We conclude that ASXL1 and TP53 mutations identify two molecular subgroups among AML-MRCs, with specific poor prognosis. This could be useful for future diagnostic and prognostic classifications.

No MeSH data available.


Related in: MedlinePlus