Loss-of-function (LoF) mutations in Polycomb repressor complexes (PRCs) affecting enhancer of zeste homolog 2 (EZH2) and Additional sex combs like 1 (ASXL1) are frequently identified in both myeloid and lymphoid neoplasms, and correlate with poor prognosis.1, 2, 3, 4, 5, 6ASXL1 exon 12 mutation resulting in frameshift and nonsense transcripts is one of the most common mutations accounting for up to 45% of patients with myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) and chronic myelomonocytic leukemia (CMML).1 The gene discussed is EZH2; the disease is myeloproliferative disorder.