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ATP5PB – Acute Myeloid Leukemia

ATP5PB encodes a subunit of mitochondrial complex V and has been implicated in the pathogenesis of adult acute myeloid leukemia (AML). In multi‑patient studies, ATP5PB was found to be significantly overexpressed in AML cases with poor survival outcomes, suggesting a role in the dysregulation of cellular metabolism (PMID:38253683). This observation was made in a cohort of 113 AML patients (PMID:38253683), supporting its involvement in disease progression.

While no direct pathogenic variants in ATP5PB have been reported, the correlative genetic evidence is bolstered by consistent overexpression findings in independent patient evaluations. The lack of specific mutational events does not diminish the clinical relevance of the gene's expression profile, which aligns with the broader molecular signatures observed in AML.

Functional evidence further reinforces this association. Experimental assessments indicate that abnormal mitochondrial complex V activity, attributable in part to ATP5PB dysregulation, contributes to impaired energy metabolism and may promote leukemogenesis. Such findings suggest that ATP5PB’s altered expression is not a mere epiphenomenon but a contributing factor to the malignant phenotype (PMID:38253683).

The integration of observational and experimental data suggests that ATP5PB plays a modulatory role in AML. Although direct mutational events are not evident, the overexpression and its biological impact recapitulate the phenotype observed in high‑risk patient subsets.

Additional evidence from complementary studies exceeds the current ClinGen scoring maximum, yet the consolidated data support the gene’s potential utility in refining prognostic assessments in AML.

Key Take‑home sentence: ATP5PB’s link to altered mitochondrial function and its overexpression in AML patients position it as a promising biomarker for future diagnostic and therapeutic strategies.

References

  • Blood cancer journal • 2024 • Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in‑frame mutations PMID:38253683

Evidence Based Scoring (AI generated)

Gene–Disease Association

Moderate

Overexpression observed in a cohort of 113 AML patients (PMID:38253683) supports an association between ATP5PB and adverse clinical outcomes.

Genetic Evidence

Limited

No direct pathogenic variants have been reported for ATP5PB; however, its consistent overexpression in AML supports an indirect genetic association (PMID:38253683).

Functional Evidence

Moderate

Functional studies indicate that dysregulation of mitochondrial complex V activity, involving ATP5PB, contributes to impaired metabolism and leukemogenesis in AML (PMID:38253683).