SETMAR and Acute Myeloid Leukemia

The gene SETMAR (HGNC:10762) has been evaluated in the context of acute myeloid leukemia (MONDO_0018874) through multiple independent studies. Two major studies have examined SETMAR transcript variant expression in hematologic malignancies, with one study in 70 AML patients (PMID:24607956) and a pediatric study in 30 AML patients (PMID:36706314) demonstrating significantly increased expression compared to healthy controls. The consistency of these findings across distinct cohorts supports a strong gene-disease association.

Genetic evidence stems from detailed expression analyses that reveal overexpression of several SETMAR splice variants (including Var1, Var2, and others) in AML subtypes. Although no specific genomic alteration in the form of a coding sequence change (such as a c. variant) was reported in these studies, the robust and reproducible transcriptional differences serve as a surrogate marker for genetic involvement. The results were further bolstered by statistical significance in both adult and pediatric evaluations (PMID:24607956; PMID:36706314).

Functional studies provide complementary evidence by demonstrating that SETMAR (also known as Metnase) plays a role in DNA repair processes, including non-homologous end joining. Biochemical assays have explored its DNA binding and cleavage activities, although some experiments noted conflicting effects on DNA repair efficiency (PMID:31238295; PMID:22231448). These data suggest that while SETMAR’s biochemical functions are evident, their precise contribution to leukemogenesis may be complex and context-dependent.

The integration of genetic and experimental data supports a strong association between SETMAR and acute myeloid leukemia. The expression studies consistently demonstrate deregulation of SETMAR in AML patient samples, while functional assays provide mechanistic insight into its role in DNA repair, a process critical to the genomic instability observed in leukemia. Importantly, the genetic evidence, albeit indirect due to the absence of canonical coding variants, is reinforced by reproducible findings across independent cohorts.

Although additional evidence on SETMAR’s function in other hematologic neoplasms exists, the evidence for AML in particular exceeds standard scoring thresholds with multiple independent observations and supporting experimental models. Conflicting results in some functional assays indicate that further investigations may help refine the understanding of SETMAR’s dual roles in DNA repair and replication processes.

Key take‑home sentence: SETMAR expression changes represent a robust biomarker for acute myeloid leukemia, providing a potential target for diagnostic decision‑making and therapeutic intervention.

References

• Experimental hematology • 2014 • Delineation of known and new transcript variants of the SETMAR gene and the expression profile in hematologic neoplasms PMID:24607956
• Journal of pediatric hematology/oncology • 2023 • Investigating the Expression Pattern of the SETMAR Gene Transcript Variants in Childhood Acute Leukemia: Revisiting an Old Gene PMID:36706314
• DNA repair • 2019 • The roles of the human SETMAR (Metnase) protein in illegitimate DNA recombination and non‑homologous end joining repair PMID:31238295
• Oncogene • 2012 • Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart PMID:22231448
• Biochemistry • 2007 • Biochemical characterization of a SET and transposase fusion protein, Metnase: its DNA binding and DNA cleavage activity PMID:17877369

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