SRSF2 mutations in myelodysplasia/myeloproliferative neoplasms

Aujla, Amandeep; Linder, Katherine; Iragavarapu, Chaitanya; Karass, Michael; Liu, Delong

doi:10.1186/s40364-018-0142-y

Cited by 15 publications

(9 citation statements)

References 80 publications

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“…For instance, point mutations and deletions in the HNRNPK gene, causing hnRNP K down-regulation, have been suggested to have a role in the development of acute myeloid leukemia (Sweetser et al, 2005;Gallardo et al, 2015). Moreover, hotspot mutations in the SRSF2 gene, such as P95H, change the binding properties of the SRSF2 protein and cause genome-wide splicing network alteration and aberrant maturation of different hnRNPs, including HNRNPA2B1, HNRNPM, HNRNPH1, and HNRNPH3, especially in myelodysplastic syndromes (Komeno et al, 2015;Arbab et al, 2018;Aujla et al, 2018;Liang et al, 2018;Masaki et al, 2019).…”

Section: Thementioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

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The spliceosomal complex components, together with the heterogeneous nuclear ribonucleoproteins (hnRNPs) and serine/arginine-rich (SR) proteins, regulate the process of constitutive and alternative splicing, the latter leading to the production of mRNA isoforms coding multiple proteins from a single pre-mRNA molecule. The expression of splicing factors is frequently deregulated in different cancer types causing the generation of oncogenic proteins involved in cancer hallmarks. Cervical cancer is caused by persistent infection with oncogenic human papillomaviruses (HPVs) and constitutive expression of viral oncogenes. The aberrant activity of hnRNPs and SR proteins in cervical neoplasia has been shown to trigger the production of oncoproteins through the processing of pre-mRNA transcripts either derived from human genes or HPV genomes. Indeed, hnRNP and SR splicing factors have been shown to regulate the production of viral oncoprotein isoforms necessary for the completion of viral life cycle and for cell transformation. Target-therapy strategies against hnRNPs and SR proteins, causing simultaneous reduction of oncogenic factors and inhibition of HPV replication, are under development. In this review, we describe the current knowledge of the functional link between RNA splicing factors and deregulated cellular as well as viral RNA maturation in cervical cancer and the opportunity of new therapeutic strategies.

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Section: Thementioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

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“…10 The use of other molecular targeted therapy such as SRSF2 inhibitor may be necessary to overcome primary resistant to the KIT inhibitor. 17,18 In conclusion, our study has demonstrated the clonal evolution of malignant cells during the progression of ASM-CMML under treatment with midostaurin and azacitidine and provided a rationale for the combinatorial molecular targeted therapy in advSM.…”

Section: Genomic Testing Was Approved By the Mackay Memorial Hospitalmentioning

confidence: 68%

Clonal evolution and heterogeneity in advanced systemic mastocytosis revealed by single-cell DNA sequencing

Lim

Huang

et al. 2021

Blood Advances

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Advanced systemic mastocytosis (advSM) is a clonal stem cell neoplasm that includes aggressive SM (ASM), SM with an associated hematologic neoplasm (AHN), and mast cell leukemia. 1-3 The median survival is 41 months for ASM, 24 months for SM-AHN, and ,6 to 18 months for mast cell leukemia. 4-6 KIT D816V mutation can be detected in .90% of SM patients. 7 Interestingly, multilineage involvement of KIT D816V and multimutations in other genes such as SRSF2, ASXL1, and RUNX1 are frequently detected in advSM. 8 Some of the above-mentioned mutations were found to precede the KIT D816V mutation, indicating that the KIT mutation is a phenotypic mutation in SM. 9 The presence and number of several mutated genes such as the SRSF2-ASXL1-RUNX1 panel are associated with worse prognosis in advSM. 10-12

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“…Loss of ASXL1 leads to an increase in apoptotic and proliferating cells, but also reduced HSC and progenitor populations (Wang et al, 2014). Mutations in the SRSF2 gene lead to growth arrest, early senescence and apoptosis in hematopoietic cells (Aujla, Linder, Iragavarapu, Karass, & Liu, 2018). These mutations combined could explain the distinct pattern of proliferative aberrancies seen in the MDS/MPN cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in the SRSF2 gene lead to growth arrest, early senescence and apoptosis in hematopoietic cells (Aujla, Linder, Iragavarapu, Karass, & Liu, 2018). These mutations combined could explain the dis- F I G U R E 3 Summary of basic characteristics and Ki-67 expression of myeloid BM malignancies.…”

Section: The Ki-67 Expression Pattern In Mds Patientsmentioning

confidence: 99%

Proliferative activity is disturbed in myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and MDS/MPN diseases. Differences between MDS and MDS/MPN

Mestrum

Wit

Drent

et al. 2020

Cytometry Part B Clinical

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The proliferation marker Ki-67 is widely used within the field of diagnostic histopathology as a prognostic marker for solid cancers. However, Ki-67 is hardly used for prognostic and diagnostic purposes in flow cytometric analyses of hematologic neoplasms. In the present study, we investigated to what extent the proliferative activity, as determined by Ki-67 expression, is disturbed in myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and MDS/MPN diseases. Bone marrow aspirates from 74 patients suffering from MPN, MDS, or MDS/MPN, and aspirates from 50 non-malignant cases were analyzed by flow cytometry for Ki-67 expression in the erythro-, myelo-, and monopoiesis. Ki-67 expression was used to investigate the proliferative activity during the various maturation steps within these hematopoietic cell lineages. In the MPN patient cohort, the proliferative activity of all cell lineages is significantly higher during almost all maturation stages compared to those of the benign control cohort. In the MDS and MDS/MPN cohort, a significantly lower proliferative activity is observed in the early maturation stages. In the MDS/MPN patient cohort, increased proliferative activity is seen in the later stages of the maturation. MDS and MDS/MPN display a distinct pattern in the proliferating fraction of maturing hematopoietic cells. This could become of added value in order to classify these malignancies based on their biological background and behavior, as well as in gaining a better understanding into the pathobiology of these malignancies.

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SRSF2 mutations in myelodysplasia/myeloproliferative neoplasms

Cited by 15 publications

References 80 publications

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Clonal evolution and heterogeneity in advanced systemic mastocytosis revealed by single-cell DNA sequencing

Proliferative activity is disturbed in myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and MDS/MPN diseases. Differences between MDS and MDS/MPN

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