The role of NPM1 alternative splicing in patients with chronic lymphocytic leukemia.

Autor: Szelest M; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Masternak M; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland.; Department of Hematology, St. John's Cancer Centre, Lublin, Poland., Zając M; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Chojnacki M; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Skórka K; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Zaleska J; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Karczmarczyk A; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Stasiak G; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Wawrzyniak E; Department of Hematology, Medical University of Lodz, Lodz, Poland., Kotkowska A; Department of Hematology, Medical University of Lodz, Lodz, Poland., Siemieniuk-Ryś M; Department of Hematology, Medical University of Lodz, Lodz, Poland., Purkot J; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland., Subocz E; Department of Hematology, Military Institute of Medicine, Warsaw, Poland.; Independent Public Health Care Center of the Ministry of Internal Affairs and Administration with the Warmian-Masurian Oncology Centre in Olsztyn, Olsztyn, Poland., Cichocka E; Department of Hematology, Copernicus Hospital, Torun, Poland., Tomczak W; Department of Hematooncology and Bone Marrow Transplantation Unit, Medical University of Lublin, Lublin, Poland., Zawirska D; Department of Hematology, Jagiellonian University, Krakow, Poland., Giannopoulos K; Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland.; Department of Hematology, St. John's Cancer Centre, Lublin, Poland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Oct 25; Vol. 17 (10), pp. e0276674. Date of Electronic Publication: 2022 Oct 25 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0276674
Abstrakt: Objectives: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with heterogeneous clinical course. Recent studies revealed a link between NOTCH1 mutation and the overexpression of MYC and MYC-related genes involved in ribosome biogenesis and protein biosynthesis, such as nucleophosmin-1 (NPM1), in CLL cells. In the present study, we aim to evaluate the impact of the NOTCH1 mutation on the MYC and MYC induced NPM1 expression in CLL cells via quantification of their transcripts.
Methods: Using qRT-PCR, we analyzed the levels of MYC and three main NPM1 splice variants in 214 samples collected from CLL patients. We assessed the impact of each splice variant on CLL prognostic markers, including the IGHV, TP53, NOTCH1, SF3B1, and MYD88 mutational status, cytogenetic aberrations, and laboratory features.
Results: Significantly higher levels of NPM1.R1 transcripts in patients with unmutated compared to mutated IGHV status were found. The median time to first treatment (TTFT) in patients with a high level of NPM1.R1 was significantly shorter compared to the group with low NPM1.R1 levels (1.5 vs 33 months, p = 0.0002). Moreover, in Multivariate Cox Proportional Hazard Regression Model NPM1.R1 splice variant provided an independent prognostic value for TTFT.
Conclusion: In conclusion, our study indicates the prognostic significance of the level of NPM1.R1 expression and suggests the importance of splicing alterations in the pathogenesis of CLL.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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