A reappraisal of ASXL1 mutation sites and the cohesin-binding motif in myeloid disease

Emerging evidence supports that ASXL1 mutation in myeloid neoplasia leads to aberrant protein gain-of-function rather than loss-of-function as initially thought [ 1 ]. Thus, a reassessment of the potential biologic relevance of the site of mutation in ASXL1 in patients with myeloid disease is warranted. To date, a large-scale comparison of patients with the c.1934dupG (p.G646Xfs*12) hotspot mutation vs. those with other ASXL1 mutations has not been performed. In addition, ASXL1 has a role in stabilizing the cohesin complex by means of a cohesin-binding motif (CBM) [ 2 ], and patients with CBM mutations have been insufficiently characterized. Thus, we sought to further characterize the clinicopathologic and genetic features of patients by ASXL1 mutation site using a large clinical dataset.