ASXL1 is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. ASXL1 functions as either a coactivator or corepressor for the retinoid receptors retinoic acid receptor (RAR) and retinoid X receptor in a cell type-specific manner. These results support predictions of dual activator/repressor functions for mammalian ASXL proteins depending on cellular context.
ASXL1 somatic mutations (insertions, deletions, substitutions) seem to be restricted to hematopoietic and lymphoid tissue tumors. Mutations have been observed in myelodysplastic syndromes (MDS), juvenile myelomonocytic leukemia (JMML), CMML (a disease classified as MDS/Myeloproliferative disorder), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), B-acute lymphoblastic leukemia (B-ALL) samples.
The most common mutation is an insertion at amino acid 646
References (open access):
Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M, Tadrist Z, Olschwang S, Vey N, Birnbaum D, Gelsi-Boyer V, Mozziconacci MJ. BMC Cancer. 2010 Aug 2;10:401.
Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Abdel-Wahab O, Manshouri T, Patel J, Harris K, Yao J, Hedvat C, Heguy A, Bueso-Ramos C, Kantarjian H, Levine RL, Verstovsek S. Cancer Res. 2010 Jan 15;70(2):447-52.