2021年11月5日 · The major amino acid alteration of NPM1 was a frameshift mutation at the 288 th histidine (W288fs*12). Patterns of KMT2A(MLL)-rearrangement included MLL fusion (e.g., MLL-MLLT3) and partial tandem duplication (PTD) in ten patients each. MLL amplification was observed in three patients.

2020年11月5日 · Background: Acute myeloid leukemias with KMT2A (formerly known as MLL-1) fusion genes (MLL-AML) and those with NPM1 mutations (NPM1-AML) are distinct subtypes as defined by the WHO classification. Although they have different clinical features and prognostic impact , recent studies suggest that the MLL1 co-factor, menin, plays a key role in ...

2024年10月23日 · Nucleophosmin (NPM1) is a nucleolar protein and one of the most frequently mutated genes in acute myeloid leukemia (AML). In addition to the commonly detected frameshift...

2023年3月1日 · We uncovered an important functional role of mutant NPM1 as a crucial direct driver of oncogenic gene expression in AML. NPM1c can bind to chromatin and cooperate with the MLL complex, providing the first functional insight into the mechanism of Menin-MLL inhibition in NPM1c leukemias.

2023年3月15日 · Mutated nucleophosmin 1 gene (NPM1) is the most common genetic alteration in adult acute myeloid leukaemia (AML), occurring in up to 30% of patients 8. Currently...

2022年1月11日 · Pre-clinical studies presented here demonstrate that genetic knockout or degradation of Menin or treatment with the MI SNDX-50469 reduces MLL1/MLL1-FP targets, associated with MI-induced...

2019年11月13日 · NPM1mutant (NPM1 mut) and MLL1-rearranged (MLL-r) acute myeloid leukemias (AMLs) exhibit aberrant expression of HOX and MEIS1 transcription factors and commonly harbor an activating mutation in the receptor tyrosine kinase FLT3.

2020年11月19日 · The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and ar …

2022年1月11日 · Combined therapy with SNDX-5613 and venetoclax exerts superior in vivo efficacy in a cell line or PD AML cell xenografts harboring MLL1-r or mt-NPM1. Synergy with the MI-based combinations is preserved against MLL1-r AML cells expressing FLT3 mutation, also CRISPR-edited to introduce mtTP53.

2024年11月18日 · Here, we review the clinical development of menin inhibitors for the treatment of AML harboring mutations in the Nucleophosmin (NPM1) gene (NPM1 m) or rearrangements in the histone-lysine N-methyltransferase 2A (KMT2A) gene (KMT2A r), …