文摘
m>DNMT3Am> mutations are seen in ∼5% of patients with chronic myelomonocytic leukemia (CMML) and thus far, have had an indeterminate prognostic impact on survival. We carried out this study to assess the prognostic impact of m>DNMT3Am> mutations on a larger informative cohort of CMML patients (m>n m>=m> m>261). m>DNMT3Am> mutations were seen in 6% (m>n m>=m> m>16); 56% (m>n m>=m> m>9) male, with a median age of 64 years. Eighty-one % of m>DNMT3Am> mutations were missense, with the Arg882 mutational hot spot accounting for 63% of all changes. Five (31%) patients had an abnormal karyotype whereas concurrent gene mutations (m>SF3B1/SRSF2/U2AF1m>−56%, m>TET2m>−50%, and m>ASXL1m>−25%) were seen in all patients. Apart from a higher frequency of m>SF3B1m> (m>Pm> = 0.0001) and m>PTPN11m> (m>Pm> = 0.005) mutations and a lower frequency of m>SRSF2m> (m>Pm> = 0.004) mutations, there were no significant differences between m>DNMT3Am> mutated patients and their wildtype counterparts. In univariate analysis, survival was shorter in m>DNMT3Am> mutated (median 8 months) versus wildtype (median 27 months) patients (m>Pm> = 0.0007; HR 2.9, 95% CI 1.5–5.7); with other variables of significance including lower hemoglobin (m>Pm> = 0.002), higher leukocyte count (m>Pm> = 0.0009), higher monocyte count (m>Pm> = 0.0012), circulating blast % (m>Pm> = 0.001), circulating immature myeloid cells (m>Pm> = 0.01), bone marrow blast % (m>Pm> = 0.045), abnormal karyotype (m>Pm> = 0.02), and m>ASXL1m> (m>Pm> = 0.01) mutations. In a multivariable model that included the aforementioned variables, when both m>DNMT3Am> and m>ASXL1m> mutations were added, only m>DNMT3Am> (m>Pm> < 0.0001) and m>ASXL1m> (m>Pm> = 0.004) mutations remained significant. m>DNMT3Am> mutations were also predictive of a shortened leukemia-free survival. These findings warrant inclusion of m>DNMT3Am> mutations in molecularly integrated CMML prognostic models. Am. J. Hematol. 92:56–61, 2017.
