Evidence map›Paper›PMID 39920624›Full record

ArticleBMC cancer2025

Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia.

Fei Xie, Ting-Juan Zhang, Xin-Long Zhang, Zi-Jun Xu, Liang Qiao, Yun Wang, Yang-Jing Zhao, Jun Qian, Jing-Dong Zhou

Abstract read
In one paragraph

Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

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8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Fei Xie *Department of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China.
Ting-Juan Zhang *Department of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China.
Xin-Long Zhang *Department of Hematology, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, 212300, Jiangsu, China.
Zi-Jun XuDepartment of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China.
Liang QiaoDepartment of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China.
Yun WangDepartment of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China.
Yang-Jing ZhaoDepartment of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China.
Jun QianDepartment of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China.
Jing-Dong ZhouDepartment of Hematology, The Affiliated People's Hospital of Jiangsu University, 8 Dianli Rd, Zhenjiang, 212002, Jiangsu, China. zhoujingdong@ujs.edu.cn.

Funding

National Natural Science Foundation of China 82100183National Natural Science Foundation of China 82270179National Natural Science Foundation of China 82300164Natural Science Foundation of Jiangsu Province BK20221287Natural Science Foundation of Jiangsu Province BK20230296Research Project of Jiangsu Commission of Health M2022123Social Development Foundation of Zhenjiang SH2022027Social Development Foundation of Zhenjiang SH2023009
6 · The paper itself

Abstract

backgroundThe homeobox (HOX) genes especially for HOXA cluster play crucial roles in leukemogenesis. HOXA overexpression caused by genetic alterations, such as KMT2A rearrangements, NUP98- fusions and FLT3-ITD mutations, is frequently identified in AML. However, very few studies determined the DNA methylation-mediated epigenetic regulation of the HOXA cluster genes in AML.

methodsWe systematically first screened the prognostic value of HOXA cluster genes methylation in AML from The Cancer Genome Atlas (TCGA) datasets. Afterwards, the candidate prognosis-related gene HOXA9 were selected for clinical relevance analysis and were further validated in another independent cohort from our research center.

resultsThe methylation of HOXA9, among HOXA cluster genes, negatively correlated with adverse prognosis and expression were screened and identified in AML among TCGA datasets. Clinically, HOXA9 hypomethylation was positively correlated with specific subtypes of AML, such as French-American-British (FAB)-M5/M7, normal karyotype and FLT3, NPM1 and DNMT3A mutation, whereas negatively associated with FAB-M3, t(15;17), t(8;21) and t(16;16). Importantly, AML patients with HOXA9 hypomethylation may profit from transplantation, whereas AML patients with HOXA9 hypermethylation could not, suggesting that HOXA9 methylation may be used to guide therapeutic selection between transplantation and chemotherapy. Bioinformatics analysis demonstrated the association of HOXA9 expression with diverse leukemia-related genes (HOXAs, SOSTDC1, MEG3, miR-10a, miR-381 and miR-193b) and signaling pathways (PI3K-Akt signaling) in AML. Subsequently, we further validate the hypomethylation pattern of HOXA9 in AML patients and the epigenetic regulation of HOXA9 methylation in AML cell-lines.

conclusionsHOXA9 methylation linked to HOXA9 expression correlates with diverse genetic abnormalities of AML, such as normal karyotype, t(15;17), t(8;21), t(16;16) and FLT3, NPM1 and DNMT3A mutations. Moreover, HOXA9 hypomethylation may be associated with adverse prognosis, and may guide treatment choice in AML.

Indexed as

Biomarkers, TumorDNA MethylationEpigenesis, GeneticHomeodomain ProteinsLeukemia, Myeloid, AcuteAdultFemalefms-Like Tyrosine Kinase 3Gene Expression Regulation, LeukemicHumansMaleMiddle AgedMutationNucleophosminPrognosisBiomarkers, Tumorfms-Like Tyrosine Kinase 3homeobox protein HOXA9Homeodomain ProteinsNPM1 protein, humanNucleophosminAMLHOXAHOXA9MethylationPrognosisRegulation

Identifiers

PMID39920624
PMCPMC11806540

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.