HOXA9
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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).
- 3 · How drugs use it
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.
External identifiers
Biology
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).
- KMT2A-rearranged acute leukaemia (infant ALL; adult and therapy-related AML)
- NPM1-mutant AML
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:"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.
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