Structural screening and molecular simulation identify potential ligands against the K700E hot spot variant and functional pockets of SF3B1 to modulate splicing in myelodysplastic syndrome.

ABSTRACT: Myelodysplastic syndrome (MDS), a blood disorder with ineffective hematopoiesis and risk of transformation to acute myeloid leukemia, is characterized by recurring cytogenetic and molecular alterations. By chromosome analysis, approximately 60% of patients, carry chromosome 5 and 7 alterations, trisomy of chromosome 8 and may also present with increasingly complex karyotypes, especially in higher grade MDS (MDS with refractory anemia and increased blasts type 1 and 2). Moreover, somatic pathogenic variants in genes associated with aberrant mRNA splicing are frequently mutated with SF3B1 the most frequently mutated. In the setting of SF3B1, the K700E hot-spot mutation is present in approximately 50% of cases. Since recent studies have highlighted modulation of functional dynamics in SF3B1 b

SUBMITTER: Garcia R 

PROVIDER: S-EPMC11225765 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature