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CEBPZ and Acute Myeloid Leukemia

Evidence across multiple studies suggests a potential association between CEBPZ and acute myeloid leukemia, although the genetic data remain limited. A focused analysis in an AML subgroup with isolated trisomy 13 identified CEBPZ mutations in 2 unrelated probands (PMID:24923295), indicating a possible role for this gene in leukemogenesis. Additional large‐scale gene panel studies have included CEBPZ among several recurrently mutated genes in AML (PMID:33049054, PMID:32139296), but these reports do not provide extensive segregation or variant‐specific data. The lack of targeted functional experiments means that the pathogenic mechanism of CEBPZ in AML, whether via haploinsufficiency or a dominant effect, remains speculative. Inheritance in the context of AML is somatic rather than germline, and no familial segregation has been documented for CEBPZ variants. Although the observation of recurrent mutations supports a potential clinical role, the overall evidence falls short of a robust ClinGen classification. Additional studies, including functional assays and broader cohort analyses, are required to clearly define the clinical utility of CEBPZ testing in AML.

References

  • Blood • 2014 • Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis PMID:24923295
  • Blood advances • 2020 • Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial PMID:33049054
  • Clinical lymphoma, myeloma & leukemia • 2020 • Defining Acute Myeloid Leukemia Ontogeny in Older Patients PMID:32139296

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Limited reports indicate CEBPZ mutations in approximately 2 unrelated AML probands (PMID:24923295) with additional panel evidence from independent studies (PMID:33049054, PMID:32139296).

Genetic Evidence

Limited

Mutation screening has identified CEBPZ alterations in a small subset of AML patients without clear segregation or comprehensive variant-specific details.

Functional Evidence

Limited

There are no direct functional studies evaluating CEBPZ in AML; its inclusion in multi-gene panels provides only indirect support for a pathogenic role.