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

2021 ◽  
Vol 11 ◽  
Author(s):  
Shenon Sethi ◽  
Zachary Epstein-Peterson ◽  
Anita Kumar ◽  
Caleb Ho
Keyword(s):  
Cell Lymphoma ◽  
Current Knowledge ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Disease Evolution ◽  
Genomic Complexity ◽  
Mutational Pattern ◽  
Mantle Cell

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.

Mantle Cell Lymphoma

1999 ◽  
Vol 123 (12) ◽  
pp. 1182-1188 ◽  
Author(s):  
Rebecca C. Hankin ◽  
Susan V. Hunter
Keyword(s):  
Polymerase Chain Reaction ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Diagnostic Tests ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Diagnostic ◽  
Chain Reaction ◽  
Mantle Cell ◽  
Polymerase Chain

Abstract Objective.—This article summarizes the most useful ancillary immunohistochemical and molecular assays for use in the diagnosis of mantle cell lymphoma. Data Sources.—The English language literature was surveyed, with an emphasis on recent publications, for articles presenting key advances in the molecular characterization of mantle cell lymphomas and for series of cases testing the utility of molecular diagnostic tests. The authors' series of 26 small B-cell lymphomas, analyzed for the cyclin D1 protein by paraffin immunohistochemistry and for t(11;14) by polymerase chain reaction, is included. Conclusions.—Mantle cell lymphoma, a B-cell lymphoma now recognized in the 1994 Revised European-American Classification of Lymphoid Neoplasms (REAL) classification, is a relatively aggressive lymphoma with a poor prognosis. Its characteristic t(11;14)(q13;q32) translocation has a role in oncogenesis and has been exploited for molecular diagnostic tests, but these tests vary in sensitivity, specificity, and ease of use. Improved immunohistochemical tests are sufficient to confirm the diagnosis in most cases. Conventional cytogenetics and molecular diagnostic tests for t(11;14)—Southern blot and polymerase chain reaction analysis—may be helpful in selected cases, but are laborious or of limited sensitivity. Other methods, such as fluorescence in situ hybridization, need further development to provide faster, more sensitive diagnosis.

Double-hit B-cell lymphomas

Blood ◽  
2011 ◽  
Vol 117 (8) ◽  
pp. 2319-2331 ◽  
Author(s):  
Sietse M. Aukema ◽  
Reiner Siebert ◽  
Ed Schuuring ◽  
Gustaaf W. van Imhoff ◽  
Hanneke C. Kluin-Nelemans ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treatment Modalities ◽  
Diagnostic Tools ◽  
Clinical Aspects ◽  
B Cell Lymphomas ◽  
Mantle Cell ◽  
Double Hit

Abstract In many B-cell lymphomas, chromosomal translocations are biologic and diagnostic hallmarks of disease. An intriguing subset is formed by the so-called double- hit (DH) lymphomas that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14;18)(q32;q21) involving BCL2. Recently, these lymphomas have received increased attention, which contributed to the introduction of a novel category of lymphomas in the 2008 WHO classification, “B cell lymphoma unclassifiable with features intermediate between DLBCL and BL.” In this review we explore the existing literature for the most recurrent types of DH B-cell lymphomas and the involved genes with their functions, as well as their pathology and clinical aspects including therapy and prognosis. The incidence of aggressive B-cell lymphomas other than Burkitt lymphoma with a MYC breakpoint and in particular a double hit is difficult to assess, because screening by methods like FISH has not been applied on large, unselected series, and the published cytogenetic data may be biased to specific categories of lymphomas. DH lymphomas have been classified heterogeneously but mostly as DLBCL, the majority having a germinal center phenotype and expression of BCL2. Patients with DH lymphomas often present with poor prognostic parameters, including elevated LDH, bone marrow and CNS involvement, and a high IPI score. All studies on larger series of patients suggest a poor prognosis, also if treated with RCHOP or high-intensity treatment modalities. Importantly, this poor outcome cannot be accounted for by the mere presence of a MYC/8q24 breakpoint. Likely, the combination of MYC and BCL2 expression and/or a related high genomic complexity are more important. Compared to these DH lymphomas, BCL6+/MYC+ DH lymphomas are far less common, and in fact most of these cases represent BCL2+/BCL6+/MYC+ triple-hit lymphomas with involvement of BCL2 as well. CCND1+/MYC+ DH lymphomas with involvement of 11q13 may also be relatively frequent, the great majority being classified as aggressive variants of mantle cell lymphoma. This suggests that activation of MYC might be an important progression pathway in mantle cell lymphoma as well. Based on clinical significance and the fact that no other solid diagnostic tools are available to identify DH lymphomas, it seems advisable to test all diffuse large B-cell and related lymphomas for MYC and other breakpoints.

MicroRNA Biomarkers in Canine Diffuse Large B-Cell Lymphoma

2020 ◽  
pp. 030098582096790
Author(s):  
Nelly O. Elshafie ◽  
Naila C. do Nascimento ◽  
Nathanael I. Lichti ◽  
Andrea L. Kasinski ◽  
Michael O. Childress ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Quantitative Polymerase Chain Reaction ◽  
B Cell Lymphoma ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Lymphoma is among the most common cancer in dogs. Diffuse large B-cell lymphoma (DLBCL) is the predominant type, accounting for up to half of all cases. Definitive diagnosis of DLBCL relies on cytologic evaluation with immunophenotyping, or histopathology and immunohistochemistry when needed. A rapid and specific molecular test aiding in the diagnosis could be beneficial. Noncoding microRNAs (miRNAs) are regulators of gene expression involved in a variety of cellular processes, including cell differentiation, cell cycle progression, and apoptosis. Not surprisingly, miRNA expression is aberrant in diseases such as cancers. Their high stability and abundance in tissues make them promising biomarkers for diagnosing and monitoring diseases. This study aimed to identify miRNA signatures of DLBCL to develop ancillary molecular diagnostic tools. miRNA was isolated from formalin-fixed, paraffin-embedded lymph node tissue from 22 DLBCL and 14 nonneoplastic controls. Relative gene expression of 8 tumor-regulating miRNAs was achieved by RT-qPCR (reverse transcriptase quantitative polymerase chain reaction). The results showed downregulation of the let-7 family of miRNAs and miR-155, whereas miR-34a was upregulated in DLBCL compared to the controls. We demonstrated that the combination of expression levels of miR-34a and let-7f or of let-7b and let-7f achieved 100% differentiation between DLBCL and controls. Furthermore, let-7f alone discriminated DLBCL from nonneoplastic tissue in 97% of cases. Our results represent one step forward in search of a rapid and accurate ancillary diagnostic test for DLBCL in dogs.

scholarly journals ASH highlights 2019: “aggressive B-cell lymphoma”

2020 ◽  
Vol 13 (3) ◽  
pp. 266-269 ◽  
Author(s):  
Clemens A. Schmitt
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Individual Risk ◽  
Near Future ◽  
Aggressive B Cell Lymphoma

Summary Despite its significant cure rate, diffuse large B‑cell lymphoma (DLBCL) remains a tumor entity of unmet medical need. The 2019 meeting of the American Society of Hematology (ASH) in Orlando, Florida, presented numerous directions, whereby clinicians may expect practice-changing innovations soon or in the near future. In this ASH highlight feature on “aggressive B‑cell lymphoma”, a selection of prominent findings will be summarized. Targeted therapeutics try to meet the needs of patients subgroups that would benefit, and novel immune oncology agents now represent established treatment principles for relapsed/refractory (R/R) DLBCL. Moreover, intense research efforts have been undertaken to identify biomarkers of response. Imaging-based and molecular diagnostic tools are becoming increasingly instrumental in appraising individual risk prior to the first treatment encounter and in the early phase of induction therapy. Genomic analyses of circulating tumor DNA conducted in the peripheral blood has gained attention in terms of assigning patients to dedicated tumor subtypes, monitoring their molecular tumor burden in the course of the disease, and steering personalized treatment extensions in the near future.

New Treatment Options in Mantle Cell Lymphoma

2015 ◽  
Vol 11 (2) ◽  
pp. 134
Author(s):  
Michelle Furtado ◽  
Simon Rule ◽  
◽  
◽  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Proteasome Inhibition ◽  
Free Treatment ◽  
Mantle Cell ◽  
New Treatment ◽  
The Many ◽  
Relapsed Disease

Mantle cell lymphoma is an incurable disease that generally exhibits a poor prognosis. Recent advances in targeted therapies have increased the available treatment options, in particular for patients with relapsed disease, and offer the prospect for better long-term disease control and potentially chemotherapy-free treatment. Established therapies, such as proteasome inhibition and immunomodulatory agents, are beginning to be recognised as useful in the management of mantle cell lymphoma (MCL) alongside the many emerging classes of drugs (Bruton’s tyrosine kinase [BTK] inhibitors, phosphatidylinositol-4, 5-bisphosphate 3-kinase [PI3k] inhibitors and B cell lymphoma 2 [BCL2] inhibitors) that show promise in this disease. We review the newer agents and drug combinations available for the treatment of MCL.

scholarly journals Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmoud A. Senousy ◽  
Aya M. El-Abd ◽  
Raafat R. Abdel-Malek ◽  
Sherine M. Rizk
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Diagnostic Tools ◽  
Large B Cell Lymphoma ◽  
Non Coding Rnas ◽  
Large B Cell

AbstractThe reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein–protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.

Treatment options for mantle cell lymphoma

2015 ◽  
Vol 16 (16) ◽  
pp. 2497-2507 ◽  
Author(s):  
Piotr Smolewski ◽  
Magdalena Witkowska ◽  
Tadeusz Robak
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Mantle Cell

Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4503-4506 ◽  
Author(s):  
Anja Mottok ◽  
Christoph Renné ◽  
Marc Seifert ◽  
Elsie Oppermann ◽  
Wolf Bechstein ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Somatic Hypermutation ◽  
B Cell Lymphoma ◽  
Rare Mutations ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Follicular Lymphomas ◽  
Large B Cell

Abstract STATs are constitutively activated in several malignancies. In primary mediastinal large B-cell lymphoma and Hodgkin lymphoma (HL), inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, contribute to deregulated STAT activity. Based on indications that the SOCS1 mutations are caused by the B cell–specific somatic hypermutation (SHM) process, we analyzed B-cell non-HL and normal B cells for mutations in SOCS1. One-fourth of diffuse large B-cell lymphoma and follicular lymphomas carried SOCS1 mutations, which were preferentially targeted to SHM hotspot motifs and frequently obviously inactivating. Rare mutations were observed in Burkitt lymphoma, plasmacytoma, and mantle cell lymphoma but not in tumors of a non–B-cell origin. Mutations in single-sorted germinal center B cells were infrequent relative to other genes mutated as byproducts of normal SHM, indicating that SOCS1 inactivation in primary mediastinal large B-cell lymphoma, HL, diffuse large B-cell lymphoma, and follicular lymphoma is frequently the result of aberrant SHM.

A Rare Case of Multiple Lymphomatous Polyposis With Widespread Involvement of the Gastrointestinal Tract

2003 ◽  
Vol 127 (8) ◽  
pp. 1028-1030
Author(s):  
JoséM. Remes-Troche ◽  
Jazmín De-Anda ◽  
Víctor Ochoa ◽  
Rafael Barreto-Zuñiga ◽  
Julián Arista-Nasr ◽  
...  
Keyword(s):  
Rare Case ◽  
Chemotherapy Regimen ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Malignant Cells ◽  
Gi Tract ◽  
Diffuse Abdominal Pain ◽  
Mantle Cell ◽  
Lower Gi Bleeding ◽  
Multiple Lymphomatous Polyposis

Abstract Multiple lymphomatous polyposis (MLP) is an uncommon type of primary non-Hodgkin gastrointestinal (GI) B-cell lymphoma characterized by the presence of multiple polyps along the GI tract. Malignant cells of MLP have mantle cell characteristics and thus are considered to be the counterpart of the mantle cell lymphoma (MCL) in the GI tract. Since 1961, no more than 70 well-documented cases have been published. We report the case of 53-year-old man diagnosed as having MLP. The patient presented with diffuse abdominal pain, chronic lower GI bleeding, peripheral lymphadenopathy, and weight loss. The lymphomatous polyps extended from the esophagus to the rectum, with bone marrow infiltration. Immunohistologic findings were characteristic of MCL. The patient was treated with a combined cyclophosphamide, vincristine, and prednisone chemotherapy regimen, resulting in a partial response.

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