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MEIS1 is HOXA9's partner in keeping leukaemia cells immature. The two are switched on together in KMT2A-rearranged and NPM1-mutant leukaemia, and switched off together when a menin inhibitor works.
MEIS1 (chromosome 2p14) is a homeobox transcriptional regulator that controls PAX6, activates PF4 in complex with PBX1 or PBX2, is required for haematopoiesis, megakaryocyte lineage development and vascular patterning, and may act as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukaemias (UniProt O00470). In OnCo it is, with HOXA9, the leukaemia programme downstream of the menin-KMT2A complex that revumenib and ziftomenib silence in KMT2A-rearranged and NPM1-mutant acute leukaemia (ziftomenib mechanism: displacing KMT2A complexes from menin silences HOXA9/MEIS1 and releases the differentiation block).
In plain words · MEIS1 is HOXA9's partner in keeping leukaemia cells immature. The two are switched on together in KMT2A-rearranged and NPM1-mutant leukaemia, and switched off together when a menin inhibitor works.
MEIS1 is HOXA9's partner in keeping leukaemia cells immature. The two are switched on together in KMT2A-rearranged and NPM1-mutant leukaemia, and switched off together when a menin inhibitor works.
Like HOXA9, MEIS1 is a transcription factor without a direct inhibitor in the corpus; its fall after menin inhibition is the mechanism step the revumenib and ziftomenib records describe.
No product in this corpus aims at MEIS1 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
First described 1997. Earliest sequence paper UniProt cites for the protein: Smith J.E. Jr. et al, Genomics, 1997, "Cloning and mapping of the MEIS1 gene, the human homolog of a murine leukemogenic gene". Source.
Like HOXA9, MEIS1 is a transcription factor without a direct inhibitor in the corpus; its fall after menin inhibition is the mechanism step the revumenib and ziftomenib records describe.
Query for this target: (TITLE:"MEIS1" OR ABSTRACT:"MEIS1" OR TITLE:"Meis homeobox 1" OR ABSTRACT:"Meis homeobox 1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MEIS1, not a curated reading list.
Shares Acute myeloid leukaemia (KEGG map), Acute lymphoblastic leukaemia, Acute myeloid leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Acute lymphoblastic leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares Acute myeloid leukaemia and the tag wave5-target.
Shares NPM1 mutation, KMT2A (MLL) rearrangement, Ziftomenib, Revumenib.
Shares NPM1 mutation, Ziftomenib, Menin, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia.