Publications by authors named "L Malcovati"
Article Synopsis
- * Significant research has reshaped the understanding of MDS, uncovering key mutations in important genes and helping categorize the disease into distinct types based on these genetic changes.
- * Advances in genomic profiling and the Molecular International Prognostic Scoring System (IPSS-M) are enhancing diagnosis and treatment personalization, emphasizing the need for collaborative efforts in healthcare and research.
Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history.
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- Myelodysplastic syndromes (MDS) are blood disorders marked by irregularities in myeloid cells and low blood cell counts, often caused by genetic mutations, though classification has mostly focused on cell appearance.
- A study analyzing genomic data from over 3,200 MDS patients identified 16 distinct molecular subtypes, revealing varied clinical outcomes, with the majority of patients (86%) fitting into specific genetic groups linked to different survival rates.
- The findings suggest that understanding these genetically defined subgroups can enhance MDS classification and inform future treatment strategies, emphasizing the importance of genetic insight in managing the disease.
Splicing factor SF3B1 mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences of SF3B1 mutations in human HSCs and progenitors (HSPCs) remain unclear. Here, we identify the mis-splicing program in human HSPCs as a targetable vulnerability by precise gene editing of SF3B1 K700E mutations in primary CD34+ cells.
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- Mutations in the UBA1 gene, which are linked to VEXAS syndrome, have been found in patients with myelodysplastic syndromes (MDS), with a study identifying 7% of a cohort having specific UBA1 mutations.
- An additional sequencing analysis of a larger group revealed 1% with other potentially harmful variants, and all 40 identified patients with likely/pathogenic mutations were male with various MDS subtypes.
- Most patients with UBA1 mutations exhibited symptoms consistent with VEXAS syndrome, suggesting that routine screening for UBA1 mutations should be considered in MDS management.