Luca Malcovati1, Ilaria Ambaglio, Chiara Elena. 1. aDepartment of Molecular Medicine, University of Pavia bDepartment of Hematology Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
Abstract
PURPOSE OF REVIEW: This article will review the most recent advances in the understanding of the genetic basis of myeloid neoplasms with myelodysplasia and will discuss its clinical implications. RECENT FINDINGS: Recurrent somatic mutations have been identified in about 90% of patients with myeloid neoplasms with myelodysplasia, involving genes of RNA splicing, DNA methylation, histone modification, transcription regulation, DNA repair, signal transduction, and cohesin complex. Somatic mutations are acquired in a linear manner in a multipotent hematopoietic stem cell, resulting in a growth advantage at the stem cell level and in defective differentiation and maturation of hematopoietic precursors. Recently, evidence has been provided of age-related hematopoietic clones, driven by mutations of genes recurrently mutated in myeloid neoplasms. These hematopoietic clones may represent either premalignant clones with the potential to progress to myeloid neoplasm or small malignant clones at a preclinical stage. SUMMARY: The available evidence clearly indicates that greater understanding of the molecular basis of myeloid neoplasms with myelodysplasia has relevant implications in the classification of these disorders, as well as in predicting disease risk and response to specific treatment modalities, and may open avenues of research leading to novel therapeutic options and personalized treatment in the individual patient.
PURPOSE OF REVIEW: This article will review the most recent advances in the understanding of the genetic basis of myeloid neoplasms with myelodysplasia and will discuss its clinical implications. RECENT FINDINGS: Recurrent somatic mutations have been identified in about 90% of patients with myeloid neoplasms with myelodysplasia, involving genes of RNA splicing, DNA methylation, histone modification, transcription regulation, DNA repair, signal transduction, and cohesin complex. Somatic mutations are acquired in a linear manner in a multipotent hematopoietic stem cell, resulting in a growth advantage at the stem cell level and in defective differentiation and maturation of hematopoietic precursors. Recently, evidence has been provided of age-related hematopoietic clones, driven by mutations of genes recurrently mutated in myeloid neoplasms. These hematopoietic clones may represent either premalignant clones with the potential to progress to myeloid neoplasm or small malignant clones at a preclinical stage. SUMMARY: The available evidence clearly indicates that greater understanding of the molecular basis of myeloid neoplasms with myelodysplasia has relevant implications in the classification of these disorders, as well as in predicting disease risk and response to specific treatment modalities, and may open avenues of research leading to novel therapeutic options and personalized treatment in the individual patient.
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