PuSH - Publication Server of Helmholtz Zentrum München: Clinical presentation and differential splicing of SRSF2, U2AF1 and SF3B1 mutations in patients with acute myeloid leukemia.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Bamopoulos, S.A.* ; Batcha, A.M.N.* ; Jurinovic, V.* ; Rothenberg-Thurley, M.* ; Janke, H.* ; Ksienzyk, B.* ; Philippou-Massier, J.* ; Graf, A.* ; Krebs, S.* ; Blum, H.* ; Schneider, S.* ; Konstandin, N.* ; Sauerland, M.C.* ; Görlich, D.* ; Berdel, W.E.* ; Woermann, B.J.* ; Bohlander, S.K.* ; Canzar, S.* ; Mansmann, U.* ; Hiddemann, W.* ; Braess, J.* ; Spiekermann, K.* ; Metzeler, K.H.* ; Herold, T.

Clinical presentation and differential splicing of SRSF2, U2AF1 and SF3B1 mutations in patients with acute myeloid leukemia.

Leukemia 34, 2621–2634 (2020)

Postprint

DOI

PMC

	Open Access Green

Free by publisher: Publ. Version/Full Text online available 05/2025

Abstract
Metrics
Extra information

Previous studies demonstrated that splicing factor mutations are recurrent events in hematopoietic malignancies with both clinical and functional implications. However, their aberrant splicing patterns in acute myeloid leukemia remain largely unexplored. In this study, we characterized mutations in SRSF2, U2AF1, and SF3B1, the most commonly mutated splicing factors. In our clinical analysis of 2678 patients, splicing factor mutations showed inferior relapse-free and overall survival, however, these mutations did not represent independent prognostic markers. RNA-sequencing of 246 and independent validation in 177 patients revealed an isoform expression profile which is highly characteristic for each individual mutation, with several isoforms showing a strong dysregulation. By establishing a custom differential splice junction usage pipeline, we accurately detected aberrant splicing in splicing factor mutated samples. A large proportion of differentially used junctions were novel, including several junctions in leukemia-associated genes. In SRSF2(P95H) mutants, we further explored the possibility of a cascading effect through the dysregulation of the splicing pathway. Furthermore, we observed a validated impact on overall survival for two junctions overused in SRSF2(P95H) mutants. We conclude that splicing factor mutations do not represent independent prognostic markers. However, they do have genome-wide consequences on gene splicing leading to dysregulated isoform expression of several genes.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Myelodysplastic Syndromes; Chinese Patients; Expression; Gene; Machinery; Landscape; Prognosis; Frequency; Pathway; Aml

ISSN (print) / ISBN 0887-6924

e-ISSN 1476-5551

Journal Leukemia

Quellenangaben Volume: 34, Pages: 2621–2634

Publisher Nature Publishing Group

Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)