Prognostic Significance of ASXL1 Mutations in Acute Myeloid Leukemia: A Systematic Review and Meta-analysis

Overview

Journal Caspian J Intern Med

Specialty General Medicine

Date 2024 May 29

PMID 38807730

Authors

Maryam Sheikhi

Mehrdad Rostami

Gordon Ferns

Hossein Ayatollahi

Payam Siyadat

Yasamin Ayatollahi

Zahra Khoshnegah

Affiliations

Soon will be listed here.

Abstract

Background: Although genetic mutations in additional sex-combs-like 1 (ASXL1) are prevalent in acute myeloid leukemia (AML), their exact impact on the AML prognosis remains uncertain. Hence, the present article was carried out to explore the prognostic importance of ASXL1 mutations in AML.

Methods: We thoroughly searched electronic scientific databases to find eligible papers. Twenty-seven studies with an overall number of 8,953 participants were selected for the current systematic review. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were extracted from all studies with multivariate or univariate analysis. Pooled HRs and p-values were also calculated as a part of our work.

Results: The pooled HR for OS in multivariable analysis indicated that ASXL1 significantly diminished survival in AML patients (pooled HR: 1.67; 95% CI: 1.342-2.091).

Conclusions: ASXL1 mutations may confer a poor prognosis in AML. Hence, they may be regarded as potential prognostic factors. However, more detailed studies with different ASXL1 mutations are suggested to shed light on this issue.

References

Gagan J, Van Allen E . Next-generation sequencing to guide cancer therapy. Genome Med. 2015; 7(1):80. PMC: 4517547. DOI: 10.1186/s13073-015-0203-x. View

Yu J, Li Y, Li T, Li Y, Xing H, Sun H . Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia. Exp Hematol Oncol. 2020; 9:2. PMC: 6945703. DOI: 10.1186/s40164-019-0158-5. View

Badaat I, Mirza S, Padron E, Sallman D, Komrokji R, Song J . Concurrent mutations in other epigenetic modulators portend better prognosis in BCOR-mutated myelodysplastic syndrome. J Clin Pathol. 2019; 73(4):209-212. DOI: 10.1136/jclinpath-2019-206132. View

Hollein A, Jeromin S, Meggendorfer M, Fasan A, Nadarajah N, Kern W . Minimal residual disease (MRD) monitoring and mutational landscape in AML with RUNX1-RUNX1T1: a study on 134 patients. Leukemia. 2018; 32(10):2270-2274. DOI: 10.1038/s41375-018-0086-0. View

Carbuccia N, Trouplin V, Gelsi-Boyer V, Murati A, Rocquain J, Adelaide J . Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias. Leukemia. 2009; 24(2):469-73. DOI: 10.1038/leu.2009.218. View

Prats-Martin C, Burillo-Sanz S, Morales-Camacho R, Perez-Lopez O, Suito M, Vargas M . ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia-related changes and normal karyotype. Cancer Med. 2020; 9(11):3637-3646. PMC: 7286456. DOI: 10.1002/cam4.2947. View

Asada S, Kitamura T . Aberrant histone modifications induced by mutant ASXL1 in myeloid neoplasms. Int J Hematol. 2018; 110(2):179-186. DOI: 10.1007/s12185-018-2563-7. View

Zong X, Yao H, Wen L, Ma L, Wang Q, Yang Z . ASXL1 mutations are frequent in de novo AML with trisomy 8 and confer an unfavorable prognosis. Leuk Lymphoma. 2016; 58(1):204-206. DOI: 10.1080/10428194.2016.1179296. View

Boultwood J, Perry J, Pellagatti A, Fernandez-Mercado M, Fernandez-Santamaria C, Calasanz M . Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia. 2010; 24(5):1062-5. DOI: 10.1038/leu.2010.20. View

10.

Grossmann V, Schnittger S, Kohlmann A, Eder C, Roller A, Dicker F . A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood. 2012; 120(15):2963-72. DOI: 10.1182/blood-2012-03-419622. View

11.

Chou W, Huang H, Hou H, Chen C, Tang J, Yao M . Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood. 2010; 116(20):4086-94. DOI: 10.1182/blood-2010-05-283291. View

12.

Saika M, Inoue D, Nagase R, Sato N, Tsuchiya A, Yabushita T . ASXL1 and SETBP1 mutations promote leukaemogenesis by repressing TGFβ pathway genes through histone deacetylation. Sci Rep. 2018; 8(1):15873. PMC: 6203835. DOI: 10.1038/s41598-018-33881-2. View

13.

Genovese G, Kahler A, Handsaker R, Lindberg J, Rose S, Bakhoum S . Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014; 371(26):2477-87. PMC: 4290021. DOI: 10.1056/NEJMoa1409405. View

14.

Fisher C, Pineault N, Brookes C, Helgason C, Ohta H, Bodner C . Loss-of-function Additional sex combs like 1 mutations disrupt hematopoiesis but do not cause severe myelodysplasia or leukemia. Blood. 2009; 115(1):38-46. PMC: 2803690. DOI: 10.1182/blood-2009-07-230698. View

15.

Allan J, Roboz G, Askin G, Ritchie E, Scandura J, Christos P . CD25 expression and outcomes in older patients with acute myelogenous leukemia treated with plerixafor and decitabine. Leuk Lymphoma. 2017; 59(4):821-828. PMC: 5773411. DOI: 10.1080/10428194.2017.1352089. View

16.

Wang R, Chen C, Jing Y, Qin J, Li Y, Chen G . Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique. Cancer Med. 2020; 9(22):8457-8467. PMC: 7666719. DOI: 10.1002/cam4.3467. View

17.

Yu G, Yin C, Wu F, Jiang L, Zheng Z, Xu D . Gene mutation profile and risk stratification in AML1‑ETO‑positive acute myeloid leukemia based on next‑generation sequencing. Oncol Rep. 2019; 42(6):2333-2344. PMC: 6826310. DOI: 10.3892/or.2019.7375. View

18.

Sasaki K, Kanagal-Shamanna R, Montalban-Bravo G, Assi R, Jabbour E, Ravandi F . Impact of the variant allele frequency of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 on the outcomes of patients with newly diagnosed acute myeloid leukemia. Cancer. 2019; 126(4):765-774. DOI: 10.1002/cncr.32566. View

19.

Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly J, Morra E . New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2008; 113(13):2895-901. DOI: 10.1182/blood-2008-07-170449. View

20.

Chen X, Zhu H, Qiao C, Zhao S, Liu L, Wang Y . Next-generation sequencing reveals gene mutations landscape and clonal evolution in patients with acute myeloid leukemia. Hematology. 2021; 26(1):111-122. DOI: 10.1080/16078454.2020.1858610. View