Discussion of details on Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes is given in the below paragraph.
A variety of chronic hematological malignancies known as myelodysplastic syndromes (MDS) include dysplasia, inefficient hematopoiesis, and a varied risk of developing acute myeloid leukemia. Genes involved in RNA splicing, DNA modification, chromatin control, and cell signaling have been shown to have mutations thanks to the sequencing of MDS genomes. In order to investigate the impact of acquired mutations in the biology and clinical presentation of MDS, we sequenced 111 genes across 738 patients with MDS or closely similar neoplasms, such as chronic myelomonocytic leukemia and MDS-myeloproliferative neoplasms. One or more oncogenic mutations were present in 78% of individuals.
We find intricate patterns of pairwise gene linkage, suggestive of epistatic interactions involving spliceosome machinery and epigenetic modifiers. These data, when combined with inferences on subclonal mutations, point to a genetic "predestination" concept, according to which early driver mutations, generally affecting genes involved in RNA splicing, determine future disease evolution trajectories with distinct clinical manifestations. Whether clonal or subclonal, driver mutations exhibited the same prognostic relevance, and leukemia-free survival rapidly declined as the number of driver mutations rose. With a great deal of potential for clinical application, study of oncogenic mutations in sizable, well-characterized cohorts of patients therefore demonstrates the linkages between the cancer genome and disease biology.
What are Myeloid Disorders?
In myelodysplastic syndromes (MDS), a rare kind of blood cancer, there aren't enough healthy blood cells in the body.
Another name for it is myelodysplasia.
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