Anemia, Sideroblastic ; genetics ; Calreticulin ; genetics ; Humans ; Mutation ; Myelodysplastic-Myeloproliferative Diseases ; genetics ; Phosphoproteins ; genetics ; RNA Splicing Factors ; Ribonucleoprotein, U2 Small Nuclear ; genetics

Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic stem cell disorders with different mechanisms and diverse prognosis. The excess of ring sideroblasts (RS) is an important presentation MDS, but the mechanisms of RS appearance are obscure and the treatment of MDS-RS is intractable. Splicing factors play a very important role in the maturation process of eucaryon mRNA, recent studies indicate that there is a significant causal relationship between splicing factor 3B subunit 1 (SF3B1) mutation and the presence of ring sideroblasts. Lucubrating the downstream molecular of the mutated SF3B1 can facilitate exploring the mechanisms and new therapeutic strategies of MDS-RS.
Anemia, Sideroblastic ; etiology ; genetics ; Animals ; Humans ; Mutation ; Myelodysplastic Syndromes ; complications ; genetics ; Phosphoproteins ; genetics ; RNA Splicing Factors ; Ribonucleoprotein, U2 Small Nuclear ; genetics

BACKGROUND: Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. METHODS: Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. RESULTS: Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. CONCLUSIONS: Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.
Adolescent ; Carrier Proteins/*genetics ; Child ; Child, Preschool ; Cohort Studies ; Cytogenetic Analysis ; DNA Mutational Analysis ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Leukemia, Myeloid, Acute/*genetics/pathology ; Male ; Nuclear Proteins/*genetics ; Phosphoproteins/*genetics ; Polymorphism, Single Nucleotide ; RNA Splicing ; Ribonucleoprotein, U2 Small Nuclear/*genetics ; Ribonucleoproteins/*genetics