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This summary examines the association between HOXA7 and acute myeloid leukemia. Multiple studies have reported that HOXA7 expression is significantly increased in AML patients, particularly in the context of NPM1 mutations. In one recent investigation comprising 91 AML cases and 23 healthy controls (PMID:40058172), elevated HOXA7 levels were observed to correlate with adverse clinical parameters. Additional RNA sequencing analyses from large patient cohorts have supported these findings (PMID:34421991), strengthening the case for HOXA7 as a relevant biomarker in AML.
The overall gene–disease association is best described as moderate. The evidence primarily comes from robust expression studies in sizeable AML cohorts, although definitive causative genetic variants in HOXA7 have not been described. The correlation between HOXA7 overexpression and NPM1 mutation status in AML provides a compelling case for its involvement in the disease process, but the lack of segregation and direct mutation data limits the scoring potential.
Genetically, the evidence is largely derived from expression analyses rather than the demonstration of rare, pathogenic coding variants. No specific HGVS‐described variant was identified in the available reports, and thus the genetic evidence remains insufficient to elevate the association beyond a limited tier. Nonetheless, the consistency of HOXA7 upregulation across independent studies endorses its potential clinical relevance.
Functional evidence, while not directly linked to AML, further supports a role for HOXA7 in leukemogenesis. Epigenetic studies have noted that HOXA7 expression is susceptible to regulation by polycomb proteins and DNA methylation mechanisms (PMID:18460542). These experiments, performed in cellular and animal models, indicate that dysregulation of HOXA7 may influence gene silencing processes that are critical to malignant transformation. However, further functional validation in AML-specific systems is warranted.
There is limited evidence from segregation studies as the observed effects are based on somatic expression changes rather than inherited mutations. The absence of familial cosegregation data is not unexpected given the somatic nature of acute myeloid leukemia. Consequently, the overall evidence integrates both genetic association and functional studies, albeit with some limitations, harmonizing to support HOXA7 as a biomarker for disease stratification.
Overall, while additional work is needed to establish direct causative variants in HOXA7, its consistent overexpression in AML and regulatory involvement in key epigenetic pathways underscore its emerging diagnostic utility. Key take‑home: HOXA7 expression analysis may serve as a promising tool for risk stratification and personalized treatment in AML.
Gene–Disease AssociationModerateA study involving 91 AML cases (PMID:40058172) alongside supportive RNA sequencing analyses from large cohorts (PMID:34421991) demonstrates a significant association between HOXA7 overexpression and AML, despite the absence of definitive causative variants. Genetic EvidenceLimitedGenetic evidence is based predominantly on differential expression data without the identification of specific pathogenic variants in HOXA7. Functional EvidenceLimitedFunctional studies indicate that epigenetic regulators modulate HOXA7 expression (PMID:18460542), yet direct assays in AML-specific models remain limited. |