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Clonal cytogenetic abnormalities occur in ~\u200930% of patients, while &gt;90% have gene mutations. Mutations involving <jats:italic>TET2<\/jats:italic> (~60%), <jats:italic>SRSF2<\/jats:italic> (~50%), <jats:italic>ASXL1<\/jats:italic> (~40%) and the oncogenic <jats:italic>RAS<\/jats:italic> pathway (~30%) are frequent; while the presence of <jats:italic>ASXL1<\/jats:italic> and <jats:italic>DNMT3A<\/jats:italic> mutations and the absence of <jats:italic>TET2<\/jats:italic> mutations negatively impact over\u2010all survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk stratification<\/jats:title><jats:p>Molecularly integrated prognostic models include; the Groupe Fran\u00e7ais des My\u00e9lodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS\u2010Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift <jats:italic>ASXL1<\/jats:italic> mutations, absolute monocyte count&gt;10 \u00d7\u200910<jats:sup>9<\/jats:sup>\/L, hemoglobin &lt;10\u2009g\/dL, platelet count &lt;100\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (\u22653 risk factors), intermediate\u20102 (2 risk factors), intermediate\u20101 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97\u2009months, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk\u2010adapted therapy<\/jats:title><jats:p>Hypomethylating agents such as 5\u2010azacitidine and decitabine are commonly used, with overall response rates of ~40%\u201050% and complete remission rates of ~7%\u201017%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.25684","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T07:37:01Z","timestamp":1574062621000},"page":"97-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6998-662X","authenticated-orcid":false,"given":"Mrinal M.","family":"Patnaik","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine Mayo Clinic  Rochester 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