Mantle Cell Lymphoma with t(11;22) (q13;q11.2) an indolent clinical variant?

Marrero, William; Cruz-Chacón, Alexis; Cabanillas, Fernando

doi:10.1080/10428194.2018.1427863

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…Overall, due to rarity of cases and treatment heterogeneity of MCL with variant translocations or cryptic enhancer insertions reported in the literature, any conclusion regarding their prognoses should be interpreted with caution. The few reported cases of MCL with variant CCND1 translocations involving IGK or IGL instead of IGH mostly presented as nnMCL and followed a relatively indolent clinical course (39)(40)(41)(42)(43). However, no statistical difference in OS has been found among CCND1 translocated and non-CCND1 translocated cases.…”

Section: Variant Translocations/cryptic Enhancer Insertionsmentioning

confidence: 98%

Current Knowledge in Genetics, Molecular Diagnostic Tools, and Treatments for Mantle Cell Lymphomas

et al. 2021

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Mantle Cell lymphoma (MCL) is a mature B-cell lymphoma with a well-known hallmark genetic alteration in most cases, t (11,14)(q13q32)/CCND1-IGH. However, our understanding of the genetic and epigenetic alterations in MCL has evolved over the years, and it is now known that translocations involving CCND2, or cryptic insertion of enhancer elements of IGK or IGL gene, can also lead to MCL. On a molecular level, MCL can be broadly classified into two subtypes, conventional MCL (cMCL) and non-nodal MCL (nnMCL), each with different postulated tumor cell origin, clinical presentation and behavior, mutational pattern as well as genomic complexity. This article reviews both the common and rare alterations in MCL on a gene mutational, chromosomal arm, and epigenetic level, in the context of their contribution to the lymphomagenesis and disease evolution in MCL. This article also summarizes the important prognostic factors, molecular diagnostic tools, and treatment options based on the most recent MCL literature.

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Section: Variant Translocations/cryptic Enhancer Insertionsmentioning

confidence: 98%

Current Knowledge in Genetics, Molecular Diagnostic Tools, and Treatments for Mantle Cell Lymphomas

et al. 2021

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“…CCND1 is commonly translocated to IGH in mantle cell lymphoma (MCL). Case studies also reported MCL patients with translocations involving CCND1 or CCND2 and IGL or IGK resulting in strong overexpression of cyclin D1 or D2 [238][239][240][241][242][243]. However, in a subset of cyclin D1-negative MCL cases the underlying molecular mechanism of the disease remained unclear.…”

Section: Igk and Igl Translocations In B-cell Malignanciesmentioning

confidence: 99%

Enhancing B-Cell Malignancies—On Repurposing Enhancer Activity towards Cancer

Kasprzyk

Sura

Dzikiewicz‐Krawczyk

2021

Cancers

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B-cell lymphomas and leukemias derive from B cells at various stages of maturation and are the 6th most common cancer-related cause of death. While the role of several oncogenes and tumor suppressors in the pathogenesis of B-cell neoplasms was established, recent research indicated the involvement of non-coding, regulatory sequences. Enhancers are DNA elements controlling gene expression in a cell type- and developmental stage-specific manner. They ensure proper differentiation and maturation of B cells, resulting in production of high affinity antibodies. However, the activity of enhancers can be redirected, setting B cells on the path towards cancer. In this review we discuss different mechanisms through which enhancers are exploited in malignant B cells, from the well-studied translocations juxtaposing oncogenes to immunoglobulin loci, through enhancer dysregulation by sequence variants and mutations, to enhancer hijacking by viruses. We also highlight the potential of therapeutic targeting of enhancers as a direction for future investigation.

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“… CCND1 gene mutations —Y44D‐mutant MCL is stable and can contribute to ibrutinib resistance in MCL 51 . CCND1 mutations were observed in nonnodal MCL and were associated with ibrutinib resistance. Atypical cryptic cyclin D1‐positive MCL —In unusual cases, variant cyclin D1 translocations such as t(2;11) (p11;q13) 52 and t(11;22) (q13;q11.2) 53 can exist where the MCL cases show cyclin D1 rearrangement with light chain partners (IgK or IgL) instead of IgH but immunohistochemistry (IHC) for cyclin D1 is positive. Conventional karyotype or fusion or break‐apart FISH (fluorescent in situ hybridization) probes fail to detect variant translocations.…”

Section: Introductionmentioning

confidence: 99%

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Jain

Wang

2022

American J Hematol

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The field of mantle cell lymphoma (MCL) has witnessed remarkable progress due to relentless advances in molecular pathogenesis, prognostication, and newer treatments. MCL consists of a spectrum of clinical subtypes. Rarely, atypical cyclin D1-negative MCL and in situ MCL neoplasia are identified. Prognostication of MCL is further refined by identifying somatic mutations (such as TP53, NSD2, KMT2D), methylation status, chromatin organization pattern, SOX-11 expression, minimal residual disease (MRD), and genomic clusters. Lymphoid tissue microenvironment studies demonstrated the role of B-cell receptor signaling, nuclear factor kappa B (NF-kB), colony-stimulating factor (CSF)-1, the CD70-SOX-11 axis. Molecular mechanism of resistance, mutation dynamics, and pathogenic pathways (B-cell receptor (BCR), oxidative phosphorylation, and MYC) were identified in mediating resistance to various treatments (bruton tyrosine kinase (BTK) inhibitors [ibrutinib, acalabrutinib]. Treatment options range from conventional chemoimmunotherapy and stem cell transplantation (SCT) to targeted therapies against BTK (covalent and noncovalent), Bcl2, ROR1, cellular therapy such as anti-CD19 chimeric antigen receptor therapy (CAR-T), and most recently bispecific antibodies against CD19 and CD20. MCL patients frequently relapse. Complex pathogenesis and the management of patients with progression after treatment with BTK/Bcl2 inhibitors and CAR-T (triple-resistant MCL) remain a challenge. Next-generation clinical trials incorporating newer agents and concurrent translational and molecular investigations are ongoing. 1 | INTRODUCTION Mantle cell lymphoma (MCL) is an uncommon subtype of aggressive B cell non-Hodgkin's lymphoma (B-NHL). In 1982, Weisenburger et al. 1 first described 12 cases of malignant lymphoma with lymph node biopsies showing widened mantle zones around germinal centers in the secondary lymphoid follicles. The diagnosis of MCL 2 is now well characterized. MCL is no longer considered a single disease but is a mixed bag of various subcategories with a spectrum of molecular and clinical features. MCL patients have varied clinical presentations (generally symptomatic to an asymptomatic indolent clinical course).Advances in MCL research have significantly enhanced our understanding of pathogenesis, tumor microenvironment, 3 risk factor prognostication, 4 and molecular categories. 5 With the available treatment modalities (chemoimmunotherapy, 6 stem cell transplantation [SCT], 7 covalent and noncovalent BTK inhibitors, 8,9 bispecific antibodies, 10 an ROR1 drug conjugate, 11 and Bcl2 antagonists 12 ), the response rates and patient survival have improved. 13 The FDA approval of anti-CD19-chimeric antigen receptor therapy (CAR-T)-brexucabtagene autoleucel 14 -is a landmark

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Mantle Cell Lymphoma with t(11;22) (q13;q11.2) an indolent clinical variant?

Cited by 6 publications

References 14 publications

Current Knowledge in Genetics, Molecular Diagnostic Tools, and Treatments for Mantle Cell Lymphomas

Current Knowledge in Genetics, Molecular Diagnostic Tools, and Treatments for Mantle Cell Lymphomas

Enhancing B-Cell Malignancies—On Repurposing Enhancer Activity towards Cancer

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

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