CBFA2T3 – Acute Myeloid Leukemia

This summary reviews the association between CBFA2T3 (HGNC:1537) and acute myeloid leukemia (MONDO_0018874). Two independent case studies have provided clear genetic evidence supporting this association. In one study, a pediatric patient developed secondary AML following treatment for acute promyelocytic leukemia, with the presence of a RUNX1-CBFA2T3 fusion gene confirmed via FISH, RT-PCR, and Southern blot analyses (PMID:11999578).

A subsequent case report detailed de novo AML in a 4‑year‑old patient, where the rare t(16;21)(q24;q22) translocation generated the RUNX1-CBFA2T3 fusion gene. This fusion was observed in a series of 20 patients, with several cases presenting with eosinophilia, thereby underscoring the recurring nature and clinical significance of this genetic event (PMID:19963144).

The genetic evidence is strengthened by a consistent demonstration of the fusion transcript across independent cases. The detection methods, which include FISH and RT‑PCR, have provided robust support for the pathogenic role of the translocation in AML, satisfying key criteria such as multi‑family/series validation and concordance of molecular findings with clinical presentation.

Beyond case reports, functional assessment studies have explored the regulatory mechanisms of CBFA2T3, also known as MTG16. These studies reveal that altered transcriptional regulation mediated by disruptions in the promoter region can contribute to hematopoietic dysregulation, providing a plausible mechanism for leukemogenesis (PMID:22443175).

Although the fusion involves a chromosomal rearrangement rather than a canonical single‐nucleotide variant, the molecular delineation of the breakpoint and its recurrence among patients presents a compelling genetic case. No single nucleotide HGVS‐formatted variant was reported in the available literature for CBFA2T3 in this disease context.

In integrating the genetic and functional evidence, the recurrent identification of the RUNX1-CBFA2T3 fusion in multiple AML patients, in conjunction with functional studies demonstrating perturbation of normal hematopoietic regulation, supports a strong clinical association. The data collectively indicate that the rearrangement of CBFA2T3 plays a key role in AML pathology.

Key take‑home sentence: The consistent detection of the RUNX1-CBFA2T3 fusion and its demonstrated functional impact on hematopoiesis render this association clinically actionable for diagnostic decision-making and targeted therapy in AML.

References

• Leukemia & lymphoma • 2002 • A pediatric case of secondary leukemia associated with t(16;21)(q24;q22) exhibiting the chimeric AML1-MTG16 gene PMID:11999578
• Cancer genetics and cytogenetics • 2010 • Acute myeloid leukemia with t(16;21)(q24;q22) and eosinophilia: case report and review of the literature PMID:19963144
• BMC molecular biology • 2012 • The leukemia associated nuclear corepressor ETO homologue genes MTG16 and MTGR1 are regulated differently in hematopoietic cells PMID:22443175

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