Double‐hit lymphoma: So what?

Davies, Andrew

doi:10.1002/hon.2581

Cited by 20 publications

(23 citation statements)

References 24 publications

(32 reference statements)

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“…The revised WHO classification (4th edition) newly describes the disease entity “High‐grade B‐cell lymphoma (HGBL)” and differentiates this disease entity from preexisting related WHO entities because of its poor outcome. Although several clinical trials on HGBL‐DH/TH are ongoing, there is currently no established therapeutic regimen and an intensified chemotherapeutic regimen other than R‐CHOP may be preferable for these patients due to the aggressive clinical course of HGBL‐DH/TH . Furthermore, because the median age of HGBL‐DH/TH patients is greater than 60 years, high dose chemotherapy may not be tolerated by some of these patients due to their advanced age.…”

Section: Discussionmentioning

confidence: 99%

Abemaciclib, a CDK4/6 inhibitor, exerts preclinical activity against aggressive germinal center‐derived B‐cell lymphomas

et al. 2020

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The revised WHO classification newly defined the entities "High-grade B-cell lymphoma with MYC and BCL2, and/or BCL6 rearrangements (HGBL-DH/TH)" and "HGBL, NOS." Standard immunochemotherapy for diffuse large B-cell lymphoma (DLBCL), R-CHOP, is insufficient for HGBL patients, and there are currently no optimized therapeutic regimens for HGBL. We previously reported that CCND3, which encodes cyclin D3, harbored high mutation rates in Burkitt lymphoma (BL), HGBL and a subset of DLBCL. Furthermore, the knockdown of cyclin D3 expression was toxic to germinal center (GC)-derived B-cell lymphomas. Thus, the fundamental function of cyclin D3 is important for the pathogenesis of GC-derived B-cell lymphoma. We herein used two structurally different CDK4/6 inhibitors, palbociclib and abemaciclib, and examined their suppressive effects on cell proliferation and their ability to induce apoptosis in various aggressive B-cell lymphoma cell lines. The results obtained demonstrated that abemaciclib more strongly suppressed cell proliferation and induced apoptosis in GC-derived B-cell lymphoma cell lines than the control, but only slightly inhibited those features in activated B-cell (ABC)-like DLBCL cell lines. Palbociclib exerted partial or incomplete effects compared with the control and the effect was intermediate between abemaciclib and the control. Moreover, the effects of abemaciclib appeared to depend on cyclin D3 expression levels based on the results of the expression analysis of primary aggressive B-cell lymphoma samples. Therefore, abemaciclib has potential as a therapeutic agent for aggressive GCderived B-cell lymphomas. K E Y W O R D S B-cell lymphoma, CDK4/6 inhibitor, cyclin D3, high-grade B-cell lymphoma, MYC

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Section: Discussionmentioning

confidence: 99%

Abemaciclib, a CDK4/6 inhibitor, exerts preclinical activity against aggressive germinal center‐derived B‐cell lymphomas

et al. 2020

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Section: Introductionmentioning

confidence: 99%

“…Primary lymphoma of the male breast is an extremely rare presentation affecting males in the fourth to seventh decades of life [1,2]. To date, less than 50 cases of male breast lymphoma have been reported in the literature [1,2]. Clinical presentation of breast lymphoma in men usually resembles the more common carcinomas with a mammographically solitary well-circumscribed painless mass in the breast and/or the ipsilateral axillary lymph nodes commonly unilateral [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Double-hit lymphoma of the male breast: a case report

et al. 2020

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Background Whereas lymphoma of the female breast is already rare, lymphoma of the male breast has only anecdotally been reported. Within a study of 32 lymphoma of the breast reported between 1973 and 2014 as Burkitt lymphoma, we observed a single male case, which we report here. Case presentation A 72-years-old Caucasian man presented with a mass in his left breast. Clinical history included prior basal cell carcinoma, leiomyosarcoma, and administration of spironolactone. The reference pathology diagnosis at presentation was Burkitt lymphoma according to the Kiel Classification. The present re-investigation using fluorescence in situ hybridization revealed an IGH-MYC translocation and a break in the BCL2 locus in the tumor cells. Thus, in light of the current WHO classification, the diagnosis was revised to high-grade B-cell lymphoma with MYC and BCL2 rearrangement, Burkitt morphology (so-called “double-hit” lymphoma). Genome-wide chromosomal imbalance mapping revealed a complex pattern of aberrations in line with this diagnosis. The aberrations, including copy-number gains in chromosomes 3q and 18 and focal homozygous loss in 9p21.3, resembled typical changes of lymphomas affecting “immune-privileged” sites. Conclusion The present case adds to the understanding of the pathogenesis of male breast lymphomas, about which hardly any molecular characterization has been published yet.

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“…Recently, a new distinct entity with poor prognosis was described as "the double/triple hit lymphomas", with rearrangements of MYC and BCL-2 and/or BCL-6. In addition, patients with high expression of both Myc and Bcl-2, but lacking the identifiable rearrangements (called "double expressers") also have a poor prognosis 3 . The standard-of-care treatment in these aggressive NHLs consists of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).…”

Section: Introductionmentioning

confidence: 99%

Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma

Maes

Vlummens

et al. 2019

Blood Cancer J.

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Diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are among the most aggressive B cell non-Hodgkin lymphomas. Maternal embryonic leucine zipper kinase (MELK) plays a role in cancer cell cycle progression and is associated with poor prognosis in several cancer cell types. In this study, the role of MELK in DLBCL and MCL and the therapeutic potential of MELK targeting is evaluated. MELK is highly expressed in DLBCL and MCL patient samples, correlating with a worse clinical outcome in DLBCL. Targeting MELK, using the small molecule OTSSP167, impaired cell growth and survival and induced caspase-mediated apoptosis in the lymphoma cells. Western blot analysis revealed that MELK targeting decreased the phosphorylation of FOXM1 and the protein levels of EZH2 and several mitotic regulators, such as Cdc25B, cyclin B1, Plk-1, and Aurora kinases. In addition, OTSSP167 also sensitized the lymphoma cells to the clinically relevant Bcl-2 inhibitor venetoclax by strongly reducing Mcl1 levels. Finally, OTSSP167 treatment of A20-inoculated mice resulted in a significant prolonged survival. In conclusion, targeting MELK with OTSSP167 induced strong anti-lymphoma activity both in vitro and in vivo. These findings suggest that MELK could be a potential new target in these aggressive B cell malignancies.

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Double‐hit lymphoma: So what?

Cited by 20 publications

References 24 publications

Abemaciclib, a CDK4/6 inhibitor, exerts preclinical activity against aggressive germinal center‐derived B‐cell lymphomas

Abemaciclib, a CDK4/6 inhibitor, exerts preclinical activity against aggressive germinal center‐derived B‐cell lymphomas

Double-hit lymphoma of the male breast: a case report

Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma

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