MN1 – Acute Myeloid Leukemia

MN1 functions as an oncogenic transcriptional regulator in acute myeloid leukemia (AML), where somatic overexpression and mutations contribute to leukemogenesis. In cytogenetically normal AML (CN-AML) cohorts, MN1 transcript levels were quantified in 119 adults, revealing that higher MN1 expression independently predicted lower complete remission rates and shorter disease-free and overall survival (119 patients) (PMID:19451432). Further analysis in 136 AML patients corroborated MN1 overexpression as a negative prognostic marker, present in 47% of CN-AML and all inv(16) cases, and demonstrated its utility in minimal residual disease monitoring (PMID:27765915).

Comprehensive sequencing of 292 core-binding factor AML cases identified recurrent nonsilent MN1 mutations in 4% of patients, indicating a mutational hotspot in AML pathogenesis (PMID:31896782). No familial segregation is observed (affected relatives = 0), consistent with AML’s sporadic, somatic nature. A representative MN1 frameshift variant, c.3822del (p.Gly1275fs), disrupts the C-terminal region required for leukemic transformation, as demonstrated in murine bone marrow transduction models (PMID:23626719).

Functional studies confirm that MN1 overexpression drives myeloid proliferation and impairs differentiation through gain-of-function mechanisms. Domain mapping localized essential transforming regions between amino acids 12–458 and 1119–1273, linking MN1 structural integrity to leukemogenic potential (PMID:23626719). These data establish MN1 as an AML oncogene whose overexpression and mutations correlate with adverse clinical outcomes.

Integration of genetic and experimental evidence supports a Strong gene–disease association: MN1 alterations are recurrent across >400 AML patients, with concordant in vivo models demonstrating leukemogenicity. Genetic evidence is Strong based on overexpression and mutational data from multiple cohorts. Functional evidence is Moderate given robust murine transformation assays. Continued investigation may refine MN1-targeted therapies and improve risk stratification.

Key take-home: MN1 overexpression and mutations are clinically actionable biomarkers in AML, informing prognosis and guiding future therapeutic development.

References

• Journal of clinical oncology • 2009 • Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. PMID:19451432
• Oncotarget • 2016 • Variable but consistent pattern of Meningioma 1 gene (MN1) expression in different genetic subsets of acute myelogenous leukaemia and its potential use as a marker for minimal residual disease detection. PMID:27765915
• Leukemia • 2020 • The clinical mutatome of core binding factor leukemia. PMID:31896782
• PloS One • 2013 • Mapping of MN1 sequences necessary for myeloid transformation. PMID:23626719

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