Figure 6.
Genetic heterogeneity of MDS/MPN with ubiquitous RAS pathway mutations enrichment. (A) Prevalence of molecular groups in 536 patients with MDS/MPN color-coded by specific subtypes. The bi-TET2 group accounted for 33% of MDS/MPN cases and 42% (168/399) of CMML cases. The EZH2-ASXL1 group comprised 8% of MDS/MPN cases and 26% (10/38) of atypical chronic myeloid leukemia (aCML) cases. The majority of MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) cases (63%, 27/43) were part of the SF3B1 group. (B) Proportion of MDS/MPN (green) and MDS (blue) within each molecular group and comparison with the full cohort (top). (C) Oncoplots for each molecular group (−7/SETBP1, EZH2-ASXL1, IDH-STAG2, and bi-TET2) separating MDS/MPN (green) and MDS (blue). Each column corresponds to a patient. The presence of a mutation in each gene for each patient is color-coded by the VAF (maximum VAF if several mutations within the same gene). RAS pathway mutations include mutations in N/KRAS, CBL, NF1, and PTPN11. They were observed in 68%, 51%, 45%, and 40% of patients with MDS/MPN within groups −7/SETBP1, EZH2-ASXL1, IDH-STAG2, and bi-TET2, respectively, compared with 33%, 21%, 14%, and 15% of patients with MDS within the same groups. (D) Scatterplot representing 1 dot per patients with RAS pathway mutation, with the VAF of RAS pathway mutations on the x-axis and the maximum VAF of all other mutations in the same patient on the y-axis. (E) Monocyte level in 109/L as a function of the VAF of RAS pathway mutations in the subset of 297 patients with MDS/MPN from the same molecular groups as in panel C. (F) Median survival (dots) and interquartile range (lines) for MDS/MPN (green) and MDS (blue) within each molecular group. Patients from the bi-TET2 group had favorable OS (median, 5.5 and 3.9 years for MDS and MDS/MPN, respectively). Conversely, patients from the IDH-STAG2, EZH2-ASXL1, and −7/SETBP1 groups had dismal OS in both subsets (median, 2.1, 1.8, and 1.5 years, respectively, in MDS and 2.2, 1.1, and 2.0 years, respectively, in MDS/MPN).

Genetic heterogeneity of MDS/MPN with ubiquitous RAS pathway mutations enrichment. (A) Prevalence of molecular groups in 536 patients with MDS/MPN color-coded by specific subtypes. The bi-TET2 group accounted for 33% of MDS/MPN cases and 42% (168/399) of CMML cases. The EZH2-ASXL1 group comprised 8% of MDS/MPN cases and 26% (10/38) of atypical chronic myeloid leukemia (aCML) cases. The majority of MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) cases (63%, 27/43) were part of the SF3B1 group. (B) Proportion of MDS/MPN (green) and MDS (blue) within each molecular group and comparison with the full cohort (top). (C) Oncoplots for each molecular group (−7/SETBP1, EZH2-ASXL1, IDH-STAG2, and bi-TET2) separating MDS/MPN (green) and MDS (blue). Each column corresponds to a patient. The presence of a mutation in each gene for each patient is color-coded by the VAF (maximum VAF if several mutations within the same gene). RAS pathway mutations include mutations in N/KRAS, CBL, NF1, and PTPN11. They were observed in 68%, 51%, 45%, and 40% of patients with MDS/MPN within groups −7/SETBP1, EZH2-ASXL1, IDH-STAG2, and bi-TET2, respectively, compared with 33%, 21%, 14%, and 15% of patients with MDS within the same groups. (D) Scatterplot representing 1 dot per patients with RAS pathway mutation, with the VAF of RAS pathway mutations on the x-axis and the maximum VAF of all other mutations in the same patient on the y-axis. (E) Monocyte level in 109/L as a function of the VAF of RAS pathway mutations in the subset of 297 patients with MDS/MPN from the same molecular groups as in panel C. (F) Median survival (dots) and interquartile range (lines) for MDS/MPN (green) and MDS (blue) within each molecular group. Patients from the bi-TET2 group had favorable OS (median, 5.5 and 3.9 years for MDS and MDS/MPN, respectively). Conversely, patients from the IDH-STAG2, EZH2-ASXL1, and −7/SETBP1 groups had dismal OS in both subsets (median, 2.1, 1.8, and 1.5 years, respectively, in MDS and 2.2, 1.1, and 2.0 years, respectively, in MDS/MPN).

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