Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia
Abstract Background The 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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-13633-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861971511934976 |
|---|---|
| author | Fei Xie Ting-juan Zhang Xin-long Zhang Zi-jun Xu Liang Qiao Yun Wang Yang-jing Zhao Jun Qian Jing-dong Zhou |
| author_facet | Fei Xie Ting-juan Zhang Xin-long Zhang Zi-jun Xu Liang Qiao Yun Wang Yang-jing Zhao Jun Qian Jing-dong Zhou |
| author_sort | Fei Xie |
| collection | DOAJ |
| description | Abstract Background The 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. Methods We 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. Results The 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. Conclusions HOXA9 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. |
| format | Article |
| id | doaj-art-761e7b9dd7b74121bcc133e4a3897436 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-761e7b9dd7b74121bcc133e4a38974362025-02-09T12:41:29ZengBMCBMC Cancer1471-24072025-02-0125111210.1186/s12885-025-13633-yIdentification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemiaFei Xie0Ting-juan Zhang1Xin-long Zhang2Zi-jun Xu3Liang Qiao4Yun Wang5Yang-jing Zhao6Jun Qian7Jing-dong Zhou8Department of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong UniversityDepartment of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityDepartment of Hematology, The Affiliated People’s Hospital of Jiangsu UniversityAbstract Background The 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. Methods We 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. Results The 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. Conclusions HOXA9 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.https://doi.org/10.1186/s12885-025-13633-yHOXAHOXA9MethylationRegulationPrognosisAML |
| spellingShingle | Fei Xie Ting-juan Zhang Xin-long Zhang Zi-jun Xu Liang Qiao Yun Wang Yang-jing Zhao Jun Qian Jing-dong Zhou Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia BMC Cancer HOXA HOXA9 Methylation Regulation Prognosis AML |
| title | Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia |
| title_full | Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia |
| title_fullStr | Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia |
| title_full_unstemmed | Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia |
| title_short | Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia |
| title_sort | identification of hoxa9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia |
| topic | HOXA HOXA9 Methylation Regulation Prognosis AML |
| url | https://doi.org/10.1186/s12885-025-13633-y |
| work_keys_str_mv | AT feixie identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT tingjuanzhang identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT xinlongzhang identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT zijunxu identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT liangqiao identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT yunwang identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT yangjingzhao identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT junqian identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia AT jingdongzhou identificationofhoxa9methylationasanepigeneticbiomarkerpredictingprognosisandguidingtreatmentchoiceinacutemyeloidleukemia |