In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 10 ( 2022-10-25), p. e0276674-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0276674
DOI:
10.1371/journal.pone.0276674.g001
DOI:
10.1371/journal.pone.0276674.g002
DOI:
10.1371/journal.pone.0276674.g003
DOI:
10.1371/journal.pone.0276674.g004
DOI:
10.1371/journal.pone.0276674.t001
DOI:
10.1371/journal.pone.0276674.t002
DOI:
10.1371/journal.pone.0276674.s001
DOI:
10.1371/journal.pone.0276674.s002
DOI:
10.1371/journal.pone.0276674.s003
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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