MEIS1
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.
Overview
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).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
External identifiers
Biology
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.
- KMT2A-rearranged acute leukaemia
- NPM1-mutant AML
- Haematopoietic stem cells and megakaryocyte lineage (normal function)
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery 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.
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