Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases

Abstract

The ASXL1 gene is one of the most frequently mutated genes in malignant myeloid diseases. The ASXL1 protein belongs to protein complexes involved in the epigenetic regulation of gene expression. ASXL1 mutations are found in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). They are generally associated with signs of aggressiveness and poor clinical outcome. Because of this, a systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment.

Figure 1

Distribution of ASXL1 mutations along the protein. From top to bottom are shown the localization of the ASXL1 gene on chromosome region 20q11, the exon structure of ASXL1, and the ASXL1 protein with its conserved motifs and binding regions: HARE helix-turn-helix at the N-terminus, HP1/CBX5 binding region, ASXH, an α-helical domain that contains LXXLL (nuclear receptor boxes), and the C-terminal plant homeodomain (PHD) finger. Below reported mutations (see Table 1) are shown along the protein: circles and triangles indicate frameshift and nonsense mutations, respectively, and the colors correspond to the exon location.