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MYELODYSPLASTIC NEOPLASM

Characteristics of patients with myelodysplastic neoplasm and spliceosome mutations

Leukemia volume 37, pages 1397–1400 (2023)Cite this article

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Spliceosome mutations (SM) are found in over 60% of patients with myelodysplastic neoplasm (MDS) [1]. Splicing is a critical mechanism in post-translational mRNA processing. Mutations in SF3B1, U2AF1, SRSF2, and ZRSR2 occur early and are frequently described in MDS [2]. The prognosis of MDS with SM is contentious and further complicated by factors such as clinical heterogeneity, cytogenetic features, and mutational partners. SF3B1, SRSF2, and U2AF1 encode components of the major spliceosome and have been the subject of many recent publications [3,4,5]. SF3B1 mutations confer a better prognosis, while SRSF2 and U2AF1 were weighed as poor prognostic indicators in the IPSS-M model [6]. This study aims to describe the clinical, laboratory, cytogenetic, and molecular characteristics of patients with mutant SF3B1, SRSF2, U2AF1, and ZRSR2 and their prognostic effect.

We included patients 18 years and older from 2017 to 2022 diagnosed with MDS at MDACC using the WHO 2022 criteria [7]. This was when an 81-gene next-generation sequencing panel became the institutional standard. Clinical and laboratory data were obtained from retrospective clinical record reviews. Patients with chronic myelomonocytic leukemia were excluded. This analysis followed MDACC institutional guidelines, and informed consent was obtained in accordance with the Declaration of Helsinki.

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Fig. 1: Overall survival for patients with any SM and for patients with each SM.
Fig. 2: Risk of death for co-mutational subgroups.

Data availability

Data are available from the corresponding author on reasonable request.

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Acknowledgements

This study was funded by the University of Texas MD Anderson Cancer Center Support Grant (CA016672) and the University of Texas MD Anderson Cancer Center Myelodysplastic Syndromes/Acute Myeloid Leukemia Moon Shot. We thank the patients who participated in this trial, their families, and the clinical and research staff at MD Anderson Cancer Center.

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Authors and Affiliations

  1. Department of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA

    Samuel Urrutia

  2. Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA

    Ziyi Li

  3. Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA

    Emmanuel Almanza, Alex Bataller, Jayastu Senapati, Koji Sasaki, Kelly Chien, Guillermo Montalban-Bravo, Courtney DiNardo, Gautam Borthakur, Sherry Pierce, Hagop Kantarjian & Guillermo Garcia-Manero

  4. Department of Hematopathology, MD Anderson Cancer Center, Houston, TX, USA

    Rashmi Kanagal-Shamanna & Carlos Bueso-Ramos

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  1. Samuel Urrutia
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Contributions

SU drafted the manuscript and interpreted the results. ZL and SU analyzed data. KS extracted data and developed an early project. EA and AB provided early analysis feedback. RK-S and CB-R were responsible for the genomic assessment. JS and CD provided feedback on spliceosome mutations. KC, GM-B, GB, and HK provided feedback on the manuscript. SP provided database support. GG-M oversaw the project and provided annotated feedback on the final analysis.

Corresponding author

Correspondence to Guillermo Garcia-Manero.

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The authors declare no competing interests.

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Urrutia, S., Li, Z., Almanza, E. et al. Characteristics of patients with myelodysplastic neoplasm and spliceosome mutations. Leukemia 37, 1397–1400 (2023). https://doi.org/10.1038/s41375-023-01899-9

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