Comparison of SF3B1/DNMT3A Comutations With DNMT3A or SF3B1 Mutation Alone in Myelodysplastic Syndrome and Clonal Cytopenia of Undetermined Significance

Song, Jinming; Hussaini, Mohammad; Qin, Dahui; Zhang, Mengjie; Shao, Haipeng; Zhang, Ling; Gajzer, David; Basra, Pukhraz; Moscinski, Lynn C.; Zhang, Hailing

doi:10.1093/ajcp/aqaa016

Cited by 6 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SF3B1 emerges to be the only gene for which somatic mutations are associated with a good prognosis in MDS [16]. Our results intently aligned with published reports [17,11] as our patients harbouring the frameshift mutations of SF3B1 showed improved clinical outcome with event-free survival. Furthermore, one patient with a distinct stop-gained frameshift mutation (Y634X) showed worse prognosis and succumbed to the disease during the follow-up period.…”

Section: Discussionsupporting

confidence: 89%

“…A study by Martin et al [10] showed worse overall survival (OS) with increased tendency for disease progression in patients who carried double mutation of DNMT3A and SF3B1. However, Song et al [11] ascertained that DNMT3A/SF3B1 double mutation showed a better prognosis than patients with DNMT3A single mutation. However, data on the impact of DNMT3A/ASXL1 and DNMT3A/TET2 co-mutation on the patients' prognosis in MDS is scarce.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DNMT3A Co-Mutation with SF3B1, ASXL1 and TET2 in Indian Patients with Myelodysplastic Syndrome (MDS)

Beevi¹,

Yadav²,

Verma³

et al. 2022

BMB

View full text Add to dashboard Cite

Myelodysplastic syndrome (MDS) encompasses a diverse group of closely related clonal hematopoietic disorders.Several genes are often mutated in MDS, of which only five (DNMT3A, SF3B1, ASXL1, TET2 and SRSF2) are known to be mutated in >10% of cases. In this perspective, we studied the frequency of somatic mutations in DNMT3A, SF3B1, ASXL1 and TET2 genes and also the impact of DNMT3A co-mutation with SF3B1, ASXL1 and TET2 genes in a series of 21 Indian patients primarily diagnosed with MDS. Patients with de novo MDS were examined for mutations in DNMT3A, SF3B1, ASXL1 and TET2 genes by Sanger's sequencing. The prognostic impact of DNMT3A mutations was evaluated in juxtaposition with SF3B1, ASXL1 and TET2 gene. Around 62% patients (13 out of 21) were found to have a somatic mutation in at least one of the genes studied herein. Of the 13 patients, 2 patients had single mutation of DNMT3A, 5 carried SF3B1 mutation and one patient each had ASXL1 and TET2 mutation. Likewise, 2 patients carried double mutation of DNMT3A/TET2 and one each carried DNMT3A/SF3B1 and DNMT3A/ASXL1 co-mutation. Our study identified novel missense, nonsense and frameshift mutations in DNMT3A, SF3B1, ASXL1 and TET2 genes for the first time in Indian MDS patients. Distinct mutations of DNMT3A in juxtaposition with SF3B1, ASXL1 and TET2 gene were predictive of clinical status.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

DNMT3A Co-Mutation with SF3B1, ASXL1 and TET2 in Indian Patients with Myelodysplastic Syndrome (MDS)

Beevi¹,

Yadav²,

Verma³

et al. 2022

BMB

View full text Add to dashboard Cite

show abstract

“…Mutations in SF3B1 have been implicated as common drivers of hematologic malignancies. Somatic SF3B1 mutations are found in approximately 30% of patients with MDS and as many as 80% of patients with the MDS subtype characterized by ring sideroblasts (MDS-RARS) [ 41 , 56 , 57 ] . These mutations are also present in 20% of patients with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) [ 41 ] and in 15% of patients with chronic myeloid leukemia (CLL) [ 58 – 60 ] .…”

Section: Sf3b1 Mutations In Cancermentioning

confidence: 99%

The biological function and clinical significance of SF3B1 mutations in cancer

et al. 2020

View full text Add to dashboard Cite

Spliceosome mutations have become the most interesting mutations detected in human cancer in recent years. The spliceosome, a large, dynamic multimegadalton small nuclear ribonucleoprotein composed of small nuclear RNAs associated with proteins, is responsible for removing introns from precursor mRNA (premRNA) and generating mature, spliced mRNAs. SF3B1 is the largest subunit of the spliceosome factor 3b (SF3B) complex, which is a core component of spliceosomes. Recurrent somatic mutations in SF3B1 have been detected in human cancers, including hematological malignancies and solid tumors, and indicated to be related to patient prognosis. This review summarizes the research progress of SF3B1 mutations in cancer, including SF3B1 mutations in the HEAT domain, the multiple roles and aberrant splicing events of SF3B1 mutations in the pathogenesis of tumors, and changes in mutated cancer cells regarding sensitivity to SF3B small-molecule inhibitors. In addition, the potential of SF3B1 or its mutations to serve as biomarkers or therapeutic targets in cancer is discussed. The accumulated knowledge about SF3B1 mutations in cancer provides critical insight into the integral role the SF3B1 protein plays in mRNA splicing and suggests new targets for anticancer therapy.

show abstract

“…These mutations, together with those of SRSF2 and SF3B1, account for about 70% of cases. [12][13][14] In general, CCUS and other premalignant cytopenias differ from MDS by the lack of myelodysplastic features or increased blasts. Acquisition of additional mutations and dysplasia 15 may eventually lead to MDS (Figure 1).…”

Section: Premalignant Clonal Cytopenias and Myelodysplastic Syndromes...mentioning

confidence: 99%

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Falini

Martelli

2023

American J Hematol

View full text Add to dashboard Cite

Several editions of the World Health Organization (WHO) classifications of lympho‐hemopoietic neoplasms in 2001, 2008, and 2016 served as the international standard for diagnosis. Since the 4th WHO edition, here referred as WHO‐HAEM4, significant clinico‐pathological, immunophenotypic, and molecular advances have been made in the field of myeloid neoplasms, which have contributed to refine diagnostic criteria, to upgrade entities previously defined as provisional and to identify new entities. This process has resulted in two recent classification proposals of myeloid neoplasms: the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, with a focus on adult myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML). The goal is to provide a tool to facilitate the work of pathologists, hematologists and researchers involved in the diagnosis and treatment of these hematological malignancies.

show abstract

Comparison of SF3B1/DNMT3A Comutations With DNMT3A or SF3B1 Mutation Alone in Myelodysplastic Syndrome and Clonal Cytopenia of Undetermined Significance

Cited by 6 publications

References 38 publications

DNMT3A Co-Mutation with SF3B1, ASXL1 and TET2 in Indian Patients with Myelodysplastic Syndrome (MDS)

DNMT3A Co-Mutation with SF3B1, ASXL1 and TET2 in Indian Patients with Myelodysplastic Syndrome (MDS)

The biological function and clinical significance of SF3B1 mutations in cancer

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Contact Info

Product

Resources

About