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HOXA9 is an embryonic growth gene that some leukaemias keep switched on so their cells never mature. Menin inhibitors such as revumenib and ziftomenib do not touch HOXA9 itself; they pull menin off the DNA so the gene switches off and the cells grow up.
HOXA9 (chromosome 7p15.2) is a sequence-specific homeobox transcription factor of the anterior-posterior patterning system that also induces E-selectin and VCAM1 on inflamed endothelium and increases EIF4E-mediated mRNA export and the translation of ODC mRNA (UniProt P31269). The menin-KMT2A pathway record explains its place in leukaemia: KMT2A fusions (infant ALL, about 10% of adult AML) and mutant NPM1 (about 30% of adult AML) are tethered to chromatin through menin and keep HOXA9 and MEIS1 transcribed, holding the cell in a stem-like state. In OnCo, revumenib and ziftomenib occupy the KMT2A-binding pocket of menin, evict the complex, HOXA9 and MEIS1 transcription falls within days and blasts differentiate into mature myeloid cells, with differentiation syndrome as the class toxicity.
In plain words · HOXA9 is an embryonic growth gene that some leukaemias keep switched on so their cells never mature. Menin inhibitors such as revumenib and ziftomenib do not touch HOXA9 itself; they pull menin off the DNA so the gene switches off and the cells grow up.
HOXA9 is an embryonic growth gene that some leukaemias keep switched on so their cells never mature. Menin inhibitors such as revumenib and ziftomenib do not touch HOXA9 itself; they pull menin off the DNA so the gene switches off and the cells grow up.
HOXA9 is not directly druggable in the corpus; the menin inhibitors act on the scaffold that keeps it expressed, and MEIS1 is its cofactor in the same programme (UniProt O00470).
No product in this corpus aims at HOXA9 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 1989. Earliest sequence paper UniProt cites for the protein: Acampora et al, Nucleic Acids Res, 1989, "The human HOX gene family". Source.
HOXA9 is not directly druggable in the corpus; the menin inhibitors act on the scaffold that keeps it expressed, and MEIS1 is its cofactor in the same programme (UniProt O00470).
Query for this target: (TITLE:"HOXA9" OR ABSTRACT:"HOXA9" OR TITLE:"HOX1G" OR ABSTRACT:"HOX1G" OR TITLE:"HOX1" OR ABSTRACT:"HOX1" OR TITLE:"homeobox A9" OR ABSTRACT:"homeobox A9") 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 HOXA9, not a curated reading list.
Shares Acute myeloid leukaemia (KEGG map), Acute lymphoblastic leukaemia, Acute myeloid leukaemia and the tag wave5-target.
Shares Epigenetic reprogramming, Acute myeloid leukaemia and the tag wave5-target.
Shares Epigenetic reprogramming 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.