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Clonal cytogenetic abnormalities occur in ~30% of patients, while &gt;90% have somatic 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 overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk\u2010Stratification<\/jats:title><jats:p>Molecularly integrated prognostic models include the Groupe Fran\u00e7ais des My\u00e9lodysplasies, Mayo Molecular Model (MMM), and the CMML specific prognostic model. Risk factors incorporated into the MMM include presence of truncating <jats:italic>ASXL1<\/jats:italic> mutations, absolute monocyte count &gt;10\u00a0\u00d7\u200910<jats:sup>9<\/jats:sup>\/L, hemoglobin &lt;10\u00a0g\/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%\u201350% and complete remission rates of ~7%\u201317%; 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.26455","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T16:56:35Z","timestamp":1641401795000},"page":"352-372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Chronic myelomonocytic leukemia: 2022 update on diagnosis, risk stratification, and management"],"prefix":"10.1002","volume":"97","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 Minnesota 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