Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia
Abstract Background The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing...
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doaj-f059dd287ce04d3a9a57b288777b05172021-10-10T11:48:37ZengBMCCancer Cell International1475-28672021-10-012111910.1186/s12935-021-02233-yRisk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemiaYi Fan0Linxiao Liao1Yajun Liu2Zhenzhen Wu3Chong Wang4Zhongxing Jiang5Shujuan Wang6Yanfang Liu7Department of Hematology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Intensive Care Unit, Zhongshan People’s HospitalDepartment of Orthopaedics, Brown University, Warren Alpert Medical School/Rhode Island HospitalDepartment of Hematology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hematology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hematology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hematology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Hematology, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. Methods We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Results In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. Conclusions Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.https://doi.org/10.1186/s12935-021-02233-yAcute myeloid leukemiaASXL1 mutationsPrognosisAllogenic hematopoietic stem cell transplantation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yi Fan Linxiao Liao Yajun Liu Zhenzhen Wu Chong Wang Zhongxing Jiang Shujuan Wang Yanfang Liu |
spellingShingle |
Yi Fan Linxiao Liao Yajun Liu Zhenzhen Wu Chong Wang Zhongxing Jiang Shujuan Wang Yanfang Liu Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia Cancer Cell International Acute myeloid leukemia ASXL1 mutations Prognosis Allogenic hematopoietic stem cell transplantation |
author_facet |
Yi Fan Linxiao Liao Yajun Liu Zhenzhen Wu Chong Wang Zhongxing Jiang Shujuan Wang Yanfang Liu |
author_sort |
Yi Fan |
title |
Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia |
title_short |
Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia |
title_full |
Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia |
title_fullStr |
Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia |
title_full_unstemmed |
Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia |
title_sort |
risk factors affect accurate prognosis in asxl1-mutated acute myeloid leukemia |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2021-10-01 |
description |
Abstract Background The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. Methods We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Results In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. Conclusions Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation. |
topic |
Acute myeloid leukemia ASXL1 mutations Prognosis Allogenic hematopoietic stem cell transplantation |
url |
https://doi.org/10.1186/s12935-021-02233-y |
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