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CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL

Antonin Bouroumeau^1,2,3, Lucile Bussot^2,4, Sieme Hamaidia^2,5

¹Department of Pathology, Grenoble-Alpes University Hospital, 38000 Grenoble, France.

|December 10, 2021

Summary

New research identifies CYCLON and NPM1 proteins as key predictors of treatment resistance in diffuse large B-cell lymphoma (DLBCL). Their specific locations within cells indicate a higher risk of refractory disease, guiding future therapies.

Area of Science:

Hematology
Oncology
Molecular Biology

Background:

Diffuse large B-cell lymphoma (DLBCL) treatment with R-CHOP immunotherapy has improved outcomes, yet a significant portion of patients experience refractory disease or relapse.
Current prognostic markers often fail to accurately stratify high-risk DLBCL patients.
Previous studies linked the nuclear protein CYCLON to DLBCL progression and immunotherapy resistance.

Purpose of the Study:

To elucidate the biological role and interaction network of CYCLON in DLBCL.
To investigate the potential role of NPM1, a nucleolar protein, in DLBCL treatment resistance.
To evaluate CYCLON and NPM1 as prognostic markers for DLBCL, particularly in relation to R-CHOP therapy.

Main Methods:

Characterization of the CYCLON protein interaction network.
Analysis of CYCLON's connection to nucleolus, RNA processing, MYC signaling, and cell cycle.
Immunohistochemistry evaluation of CYCLON and NPM1 expression and sub-cellular localization in DLBCL patient cohorts.

Main Results:

CYCLON interacts with proteins involved in RNA processing, MYC signaling, and cell cycle progression.
NPM1 emerged as a potential target linked to treatment resistance in DLBCL.
Co-expression of CYCLON and NPM1 strongly correlates with inferior prognosis in DLBCL patients.
Alternative sub-cellular localizations (extra-nucleolar CYCLON, pan-cellular NPM1) are independent predictors of R-CHOP refractory DLBCL.

Conclusions:

CYCLON and NPM1 play a significant role in DLBCL pathogenesis and treatment resistance.
Their specific sub-cellular localization patterns can predict refractory disease in DLBCL patients treated with R-CHOP.
These findings may guide risk-adapted treatment strategies and the development of novel targeted therapies for high-risk DLBCL.

Keywords:

CYCLON NPM1 R-CHOP R-IPI nucleolus prognosis

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