SRSF2 mutations in myelodysplasia/ myeloproliferative neoplasms

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

doi:10.1186/s40364-018-0142-y

SRSF2 mutations in myelodysplasia/ myeloproliferative neoplasms

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

Research output: Contribution to journal › Review article › peer-review

20 Scopus citations

Abstract

Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach. E7107, a spliceosome inhibitor, has been shown to differentially inhibit splicing more in SRSF2-mutant cells leading to decreased leukemia burden in mice. H3B-8800 is a small molecule modulator of spliceosome complex and has been shown to lower leukemia burden in SRSF2-P95H mutant mice. This review focuses on the incidence of mutant SRSF2 across various MMOS as well as recent clinical development of spliceosome inhibitors.

Original language	English
Article number	29
Journal	Biomarker Research
Volume	6
Issue number	1
DOIs	https://doi.org/10.1186/s40364-018-0142-y
State	Published - 2018

Bibliographical note

Publisher Copyright:
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

ASJC Scopus subject areas

Molecular Medicine
Clinical Biochemistry
Biochemistry, medical

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abstract = "Recurrent gene mutations have been described with varying frequencies in myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndromes (MMOS). Recent work has placed significant focus on understanding the role of gene lesions involving the spliceosomal machinery in leukemogeneis. SRSF2 is a gene encoding critical spliceosomal proteins. SRSF2 mutations appear to play an important role in pathogenesis of MMOS, particularly in chronic myelomonocytic leukemia. Inhibition of splicing may be a new therapeutic approach. E7107, a spliceosome inhibitor, has been shown to differentially inhibit splicing more in SRSF2-mutant cells leading to decreased leukemia burden in mice. H3B-8800 is a small molecule modulator of spliceosome complex and has been shown to lower leukemia burden in SRSF2-P95H mutant mice. This review focuses on the incidence of mutant SRSF2 across various MMOS as well as recent clinical development of spliceosome inhibitors.",

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AU - Karass, Michael

AU - Liu, Delong

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SRSF2 mutations in myelodysplasia/ myeloproliferative neoplasms

Abstract

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ASJC Scopus subject areas

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