Menin inhibitors are targeted agents currently in clinical development for the treatment of genetically defined subsets of acute leukemia: AML, ALL.
Menin has a tumor suppressor function in endocrine glands.
Menin it is an important co-factor for certain transcription factors and processes.
They play a key role in regulating gene transcription.
They target epigenetic modifiers.
Menin inhibitors reprogram leukemia cells back to a normal state by shutting down the gene expression programs responsible for causing leukemia.
Germ-line mutations in the gene encoding menin cause the multiple endocrine neoplasia type 1 (MEN1) syndrome, a hereditary condition associated with tumors of the endocrine glands.
Menin is also critical for leukemogenesis in subsets driven by rearrangement of the lysine methyltransferase 2A (KMT2A) gene, previously known as mixed-lineage leukemia (MLL), which encodes an epigenetic modifier.
Leukemias with rearrangements of KMT2A (KMT2Ar) are susceptible to menin inhibition.
These leukemias affect infants, children and adults, and lead to adverse outcomes with current standard therapies.
Targets in acute leukemia that are susceptible to menin inhibition, such as mutated nucleophosmin 1 (NPM1mt), t he most common genetic alteration in adult acute myeloid leukemia (AML).
Menin inhibitors are in clinical development, but common side effects include the differentiation syndrome.