Update on the molecular biology of mantle cell lymphoma

Bertoni, Francesco; Rinaldi, Andrea; Zucca, Emanuele; Cavalli, F.

doi:10.1002/hon.767

Cited by 89 publications

(76 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…124,125 Chromosomal translocation is a common genetic event in the pathogenesis of B-cell lymphomas, 126 especially mantle cell lymphoma (MCL), a mature B-cell M Monographs malignancy that constitutes 5% to 10% of non-Hodgkin lymphomas. This disease is characterized by the t(11;14) (q13;q32) translocation that juxtaposes the cyclin D1 gene (CCND1) to the immunoglobulin (Ig) heavy chain gene 127 and results in constitutive overexpression of cyclin D1 under the control of an active Ig locus. In a similar manner, the t(6;14)(p21.1;q32.3) chromosomal translocation has been reported in multiple myeloma 128 and in several subtypes of mature B-cell malignancies including diffuse large B-cell lymphoma.…”

Section: Genomic Alterations Of D-type Cyclins In Human Cancermentioning

confidence: 99%

CDK4: A Key Player in the Cell Cycle, Development, and Cancer

2012

View full text Add to dashboard Cite

The cell cycle is regulated in part by cyclins and their associated serine/threonine cyclin-dependent kinases, or CDKs. CDK4, in conjunction with the D-type cyclins, mediates progression through the G 1 phase when the cell prepares to initiate DNA synthesis. Although CDK4-null mutant mice are viable and cell proliferation is not significantly affected in vitro due to compensatory roles played by other CDKs, this gene plays a key role in mammalian development and cancer. This review discusses the role that CDK4 plays in cell cycle control, normal development, and tumorigenesis as well as how small molecule inhibitors of CDK4 can be used to treat disease.

show abstract

Section: Genomic Alterations Of D-type Cyclins In Human Cancermentioning

confidence: 99%

CDK4: A Key Player in the Cell Cycle, Development, and Cancer

2012

View full text Add to dashboard Cite

show abstract

“…Mantle cell lymphoma (MCL) accounts for 6% to 10% of non-Hodgkin's lymphoma and has the worst clinical outcome of all B-cell lymphomas, with a median survival of only 3 to 4 years (1 , and CD24 + . Also, MCL has the characteristic chromosomal translocation (11:14) (q13:q32) involving the Bcl-1 locus and IgH joining region, resulting in up-regulation of the cyclin D1 gene with increased cyclin D1 expression (2).…”

Section: Introductionmentioning

confidence: 99%

Targeting of sonic hedgehog-GLI signaling: a potential strategy to improve therapy for mantle cell lymphoma

Hegde

Munger

Emanuel

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Mantle cell lymphoma (MCL) has one of the worst clinical outcomes among the B-cell lymphomas, with a median survival of only 3 to 4 years. Therefore, a better understanding of the underlying mechanisms that regulate MCL proliferation/survival is needed to develop an effective therapy. Because sonic hedgehog (Shh)-GLI signaling has been shown to be important in the proliferation and survival of several cancers, and no such information is available for MCL, this study was undertaken. Our results show that the molecules associated with Shh-GLI signaling, such as PTCH and SMO receptors, and GLI1 and GLI2 target transcription factors were expressed in the human MCL cell lines and primary MCL cells from patients. Perturbation of this signaling in the presence of exogenous Shh/cyclopamine significantly (P < 0.001) influenced the proliferation of JVM2 MCL cells. Furthermore, down-regulation of GLI transcription factors using antisense oligonucleotides not only resulted in significantly (P < 0.001) decreased proliferation of the MCL cells but also significantly (P < 0.05) increased their susceptibility to chemotherapeutic drug, doxorubicin. Also, downregulation of GLI decreased cyclin D1 and BCL2 transcript levels, which suggests that these key molecules might be regulated by GLI in MCL. Thus, our results indicate a significant role for Shh-GLI signaling in the proliferation of MCL, and molecular targeting of GLI is a potential therapeutic approach to improve the treatment for MCL.

show abstract

“…It is a well-defined lymphoid neoplasm genetically characterized by the t(11;14)(q13;q32) translocation, with constitutive overexpression of cyclin D1. 1,2 Relapsed MCL responds poorly to standard antilymphoma therapies, and the median failure-free survival duration is approximately 18 months without a plateau in the survival curve. The median overall survival duration is 3-4 years.…”

Section: Introductionmentioning

confidence: 99%

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

et al. 2007

View full text Add to dashboard Cite

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor clinical outcome. Although front therapy induces a high rate of complete remission (CR), relapse is inevitable and new regimens are much needed for relapsed MCL. The proteasome inhibitor bortezomib (BTZ) induces apoptosis and sensitizes MCL cells to chemotherapy in relapsed MCL, but CR rates are low, with a short duration of response and severe toxicity. Here we evaluated whether BTZ is additive or synergistic with cyclophosphamide (CTX) and rituximab (RTX). Increasing doses of BTZ with a fixed dose of RTX and CTX (BRC regimen) resulted in markedly synergistic growth inhibition of MCL cells. BRC significantly enhanced apoptosis in MCL cell lines and primary tumor cells compared with singleagent treatment. Furthermore, western blotting analysis indicated that BRC induces apoptosis earlier via activation and cleavage of caspases-8, -9 and -3, and poly (ADP-ribose) polymerase, than single-agent treatment. The pan-caspase inhibitor completely blocked apoptosis induced by BRC. In vivo studies showed that BRC eradicated subcutaneous tumors in MCL-bearing SCID mice and significantly prolonged the longterm event-free survival in 70% of the mice. Hence, our study demonstrates that cytoreductive chemotherapy with both BTZ and anti-CD20 antibody may offer a better therapeutic modality for relapsed MCL.

show abstract

Update on the molecular biology of mantle cell lymphoma

Cited by 89 publications

References 54 publications

CDK4: A Key Player in the Cell Cycle, Development, and Cancer

CDK4: A Key Player in the Cell Cycle, Development, and Cancer

Targeting of sonic hedgehog-GLI signaling: a potential strategy to improve therapy for mantle cell lymphoma

Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo

Contact Info

Product

Resources

About