The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency induces Pelger-Huet anomaly and promotes sAML.

ABSTRACT: Approximately 30% of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML) via accumulating gene mutations. Genomic analyses reveal a complex interplay among mutant genes, with co-occurring and mutually exclusive patterns. Hyperactivation of c-MYB and deficiency of PU.1 have been linked to myeloid disorders. We report a case of AML with concurrent PU.1 and c-MYB mutations, exhibiting early onset, high blast count, chemo-resistance, indicating high-risk features, along with elevated Pelger-Huët anomaly (PHA). However, the synergistic mechanism of c-MYB and PU.1 in sAML remains unclear. Using c-Myb-hyperactivation and Pu.1-deficient double-strain (c-myb^hyper;pu.1^G242D/G242D) zebrafish, we inve

SUBMITTER: Xu S 

PROVIDER: S-EPMC11892618 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature