Fig. 1. Association between mutations modifying RAS and EZH2 aberrations in MN.

A Next-Generation Sequencing (NGS) results of 260 chronic myelomonocytic leukemia (CMML) patients studied within the Austrian Biodatabase for CMML [15] showing the distribution of mutations modifying RAS (RAS^mut; defined as mutations in KRAS and NRAS, as well as in the RAS-GTP modulators NF1, PTPN11 and CBL) and EZH2. In summary, 112/260 (43.1%) and 50/260 (19.2%) CMML patients had one or more RAS^mut or EZH2 mutation(s) (EZH2^mut), respectively. Below are the results of the database retrieval of 187 acute myeloid leukemia (AML) patients via The Cancer Genome Atlas (TCGA) [12] showing the distribution of RAS^mut and EZH2 inactivation (EZH2^inact; defined as EZH2 mutations and/or copy number losses). Every column describes one CMML or AML patient specimen. Colored fields indicate the presence of at least one mutation (for RAS^mut) or EZH2^inact, respectively. In summary, 33/187 (17.6%) and 25/187 (13.4%) AML patients had one or more RAS^mut mutation(s) or inactivation of EZH2, respectively. B Within both cohorts, EZH2 aberrations were significantly more common in patients harboring one or more RAS^mut compared to those without: 28.6%, vs. 12.2% (P = 0.001) for the CMML cohort (left), and 27.3%, vs. 10.4% (P = 0.020) for the AML cohort (right). Fisher’s exact test was employed for the statistical analysis. C Survival curves of the patients belonging to the CMML cohort (left), and the TCGA AML cohort (right). In both cohorts, RAS^mut and EZH2 aberration co-occurrence was associated with a shortened overall survival (median 14 vs 29 months and 7 vs 19 months for the CMML and AML patients, respectively). Censored events are indicated by a vertical line. A log-rank test was used for these comparisons.