Figure 3 Reconstruction of mutational... | American Society of Hematology

Figure 3

$Figure 3. Reconstruction of mutational hierarchies in MDS reveals recurrent patterns of molecular evolution with distinct disease-initiating events. Individual mutational hierarchies for MDS patients (n = 30) show that candidate “founder” mutations are enriched in gene groups affecting DNA methylation (blue background), RNA splicing (yellow background), and chromatin remodeling (red background). A “founder” clone consisting of 2 mutated genes from these groups was detected in 5 patients (orange background). In addition, 3 cases with TP53 mutations as isolated “founder” lesion have been identified (lilac background). Each tree represents a single patient. Dashed lines indicate more than one possible (sub)clonal dependency. Below each tree, the earliest and latest known clinical disease status, as assessed using the WHO criteria, is indicated. For clinically nonprogressive cases, the single known disease status is depicted. Additional patients with resolved oligoclonal hierarchies are found in supplemental Figure 3. MPN, myeloproliferative neoplasm; RA, refractory anemia; RAEB-1, refractory anemia with excess blasts subtype 1; RARS, refractory anemia with ring sideroblasts; RARS-T, RARS with thrombocytopenia; RCMD, refractory cytopenia with multilineage dysplasia.$

Reconstruction of mutational hierarchies in MDS reveals recurrent patterns of molecular evolution with distinct disease-initiating events. Individual mutational hierarchies for MDS patients (n = 30) show that candidate “founder” mutations are enriched in gene groups affecting DNA methylation (blue background), RNA splicing (yellow background), and chromatin remodeling (red background). A “founder” clone consisting of 2 mutated genes from these groups was detected in 5 patients (orange background). In addition, 3 cases with TP53 mutations as isolated “founder” lesion have been identified (lilac background). Each tree represents a single patient. Dashed lines indicate more than one possible (sub)clonal dependency. Below each tree, the earliest and latest known clinical disease status, as assessed using the WHO criteria, is indicated. For clinically nonprogressive cases, the single known disease status is depicted. Additional patients with resolved oligoclonal hierarchies are found in supplemental Figure 3. MPN, myeloproliferative neoplasm; RA, refractory anemia; RAEB-1, refractory anemia with excess blasts subtype 1; RARS, refractory anemia with ring sideroblasts; RARS-T, RARS with thrombocytopenia; RCMD, refractory cytopenia with multilineage dysplasia.

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