Patient was initially diagnosed with low-risk myelodysplastic syndrome-refractory cytopenias and multilineage dysplasia (MDS-RCMD), progressed to AML after failing hypomethylating agent therapy.
The spliceosomal component Splicing Factor 3B, subunit 1 (SF3B1) is one of the most prevalently mutated factors in the bone marrow failure disorder myelodysplastic syndrome.
Patient samples showed SF3B1K700E mutations within the ptDNA of 4 patients with acute leukemia and 3 with myelodysplastic syndrome who were known to harbor this mutation.
This model of secondary structure-dependent selection of cryptic 3'SS was found across multiple clonal processes associated with SF3B1 mutations (myelodysplastic syndrome and chronic lymphocytic leukemia).
Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.
In 2011, whole-exome sequencing studies showed recurrent somatic mutations of SF3B1 and other genes of the RNA splicing machinery in patients with myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm.