In this study, we reviewed 798 cases of MCL and identified 103 (13%) that were CD23+ by flow cytometry, all of which were positive for cyclin D1 and/or associated with CCND1/IGH.
These data suggest that expression of cyclin D1 in MCL is not controlled by ENGL2/PHD1-FOXO3A pathway and that chelation- and 2-oxoglutarate competition-mediated down-regulation of cyclin D1 in MCL cells is driven by yet unknown mechanism involving iron- and 2-oxoglutarate-dependent dioxygenases other than PHD1.
We found that ectopic expression of CCND1 in multiple human MCL cell lines resulted in increased SOX11 transcription, which correlated with increased acetylated histones H3K9 and H3K14 (H3K9/14Ac).
In conclusion, we report 3 cases of nodal PMBL, 2 of them without mediastinal mass, and expression of cyclin D1 due to copy number gains of CCND1 gene, a diagnostic pitfall with mantle cell lymphoma and DLBCL, not otherwise specified.
When cyclin D1 was overexpressed by the Eμ-cyclin D1 transgene, ATA B cells progressed to further diffused lymphoma in aged mice, including in various lymph nodes with accumulation of IgM<sup>hi</sup>IgD<sup>lo</sup>CD5<sup>+</sup>CD23<sup>-</sup>CD43<sup>+</sup> cells, resembling aggressive human mantle cell lymphoma.
Diagnosis of MCL relies on the identification of the t(11;14) translocation by FISH or the consequently aberrant expression of cyclin D1 by immunohistochemistry.
It is currently unclear how cyclin D1 overexpression and aberrant CDK4 activity affect NOXA stabilization and treatment efficacy of UPS inhibitors in MCL.
We identified recurrent mutations in genes that are well known to be functionally relevant in MCL, including ATM (37.5%), TP53 (31.3%), WHSC1 (31.3%), CCND1 (18.8%), NOTCH2 (6.3%), and CDKN2A (6.3%).
Overexpression and constitutive activation of CYCLIN D1 and Casein Kinase 2 are common features of many hematologic malignancies, including mantle cell lymphoma (MCL) and leukemias such as T-cell acute lymphoblastic leukemia (T-ALL).
In addition, cyclin D1 overexpression sensitized cells to transcription inhibitors, revealing a synthetic lethality interaction that was also observed in primary mantle cell lymphoma cases.
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma typically associated with the t(11;14) chromosomal translocation, resulting in overexpression of cyclin D1.