The past few years have witnessed rapid progress in the understanding of disease initiation in MDS. Chromosomal abnormalities are seen in about 50 % of patients, with chromosome 5, 7, 8, 11, and 20 most commonly affected. In those with normal karyotype, evidence of recurrent structural abnormalities is missed even with more sophisticated technology such as single-nucleotide polymorphism array (SNPa). In recent years, molecular alterations have deepened our perception of disease heterogeneity and reinforced the clinical observation that treatment response does not occur in stereotyped patterns. In fact, there is growing and convincing evidence that disease heterogeneity and response to treatment are strongly associated with genotypic and epigenetic abnormalities. Globally, MDS genome is impacted by specific mutations that can be classified as mutations that induce chromatin modification, mutations altering spliceosome machinery, and those affecting oncogenes and tumor suppressor genes. The link between chromosomal abnormalities, mutations, disease phenotype, and patterns of treatment response represents a promising challenge that continues to be unraveled.
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