Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients.
We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL.
We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients.
A repeat biopsy revealed MCL, pleomorphic variant, with loss of CD5 expression and extra copies of the MYC CONCLUSIONS: CCND1-IGH fusion-amplification with MYC copy number gain is extremely rare and may play a role in disease progression in a subset of MCL cases.
Whether adjusted for MCL International Prognostic Index (MIPI) or not, deletions of RB1, CDKN2A, TP53, and CDKN1B were associated with shorter overall survival (OS), similarly in both treatment arms, whereas CNAs in MYC, ATM, CDK2, CDK4, and MDM2 had no prognostic value.
The incidence and prognostic role of MYC and BCL2 rearrangements in mature B-cell lymphomas have been extensively studied, except the infrequent mantle cell lymphoma (MCL).
It is possible that in MCL patients expressing abnormal levels of MYCC together with a high expression of AURKA might offer some resistant to the conventional therapy purposes.
In human B-cell tumors, MYC rearrangements involving the 8q24 region and immunoglobulin heavy or light genes are a hallmark of Burkitt lymphoma (BL), but can also occur in other lymphoid malignancies, that include diffuse large B-cell lymphoma (DLBCL), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU), plasma cell myeloma (PCM), mantle cell lymphoma (MCL) and plasmablastic lymphoma.
Our study provides further evidence supporting the concept of "double hit" MCL with co-involvement of MYC gene rearrangement and/or amplification and CCND1 gene rearrangement.
We investigated the transcriptional and epigenetic repression of miR-29 by MYC, HDAC3, and EZH2 in mantle cell lymphoma and other MYC-associated lymphomas.
Additionally, double-hit MCL with MYC rearrangements with a highly aggressive clinical course have been reported, but no other frequent recurrent translocations have been identified.
Notably, 11 patients with leukemic MCL showed a different genomic profile than nodal cases, including 8p21.3 deletion at tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene cluster (55% versus 19%; P = .01) and gain of 8q24.1 at MYC locus (46% versus 14%; P = .015).
These abnormalities included 8p losses, suggesting the presence of an anti-oncogene in this region, rearrangements of 8q24, MYC gene, and translocations involving 8, X, and Y chromosomes, which might be significant in the pathogenesis of MCL progression.