A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia.
Anna CandoniGabriele CoppolaPublished in: Hematology reports (2024)
Menin inhibitors are new and promising agents currently in clinical development that target the HOX/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A-rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemias. The mechanism of action of this new class of agents is based on the disruption of the menin-KMT2A complex (consisting of chromatin remodeling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or with mutated NPM1. To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- cell cycle arrest
- clinical trial
- end stage renal disease
- newly diagnosed
- transcription factor
- induced apoptosis
- gene expression
- chronic kidney disease
- oxidative stress
- ejection fraction
- endoplasmic reticulum stress
- dna methylation
- cell death
- liver failure
- wild type
- drug induced
- dna damage
- peritoneal dialysis
- quality improvement
- electronic health record
- genome wide
- big data
- prognostic factors
- intensive care unit
- acute lymphoblastic leukemia
- drug delivery
- signaling pathway
- deep learning
- open label