A Unique Case of Mantle Cell Lymphoma With an Aberrant CD5−/CD10+ Immunophenotype and Typical Morphology

2008 ◽  
Vol 132 (8) ◽  
pp. 1346-1349
Author(s):  
Vathany Sriganeshan ◽  
Thomas R. Blom ◽  
David J. Weissmann
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Small Lymphocytic Lymphoma ◽  
Unique Case ◽  
Non Hodgkin Lymphoma ◽  
Cyclin D1 Protein ◽  
Mantle Cell ◽  
Typical Morphology

Abstract Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma with a poor prognosis that may be confused with less aggressive diseases, such as small lymphocytic lymphoma and follicular lymphoma. In many cases immunophenotyping, particularly analysis of reactivity for CD5 and CD10, is an important adjunct to morphology that usually distinguishes MCL from follicular lymphoma; the former is CD5+/CD10−, whereas follicular lymphoma is the reverse. We report a case of MCL, initially diagnosed as follicular lymphoma, that at presentation expressed neither CD5 nor CD10. At relapse, it was still CD5−, but CD10 was now detected. Studies for a t(11;14) translocation and CYCLIN D1 protein expression, however, permitted a revised diagnosis of MCL. An MCL with this immunophenotype and classical morphology has not been previously reported.

scholarly journals Immunohistochemical Analysis of Cyclin D1 Protein in Hematopoietic Neoplasms with Special Reference to Mantle Cell Lymphoma

1994 ◽  
Vol 85 (12) ◽  
pp. 1270-1279 ◽  
Author(s):  
Shigeo Nakamura ◽  
Masao Seto ◽  
Shogo Banno ◽  
Susumu Suzuki ◽  
Takashi Koshikawa ◽  
...  
Keyword(s):  
Special Reference ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Immunohistochemical Analysis ◽  
Cyclin D1 Protein ◽  
Mantle Cell

scholarly journals Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma

Blood ◽  
1995 ◽  
Vol 86 (7) ◽  
pp. 2715-2723 ◽  
Author(s):  
CJ de Boer ◽  
E Schuuring ◽  
E Dreef ◽  
G Peters ◽  
J Bartek ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Formalin Fixed Paraffin ◽  
Cyclin D1 Protein ◽  
Mantle Cell ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Abstract Mantle cell lymphoma (MCL) is a clinicopathologic entity that is difficult to diagnose on histopathologic criteria. Approximately 50% to 70% of MCL contain a t(11;14)(q13;q32) translocation involving the cyclin D1 gene. Irrespective of this rearrangement, almost all MCL show overexpression of the cyclin D1 gene at the mRNA level. Other B-cell non-Hodgkin's lymphomas (NHL) do not show this rearrangement or overexpression of cyclin D1. We developed an immunohistochemical assay to detect overexpression of the cyclin D1 protein on conventional formalin-fixed, paraffin-embedded biopsies using the well-defined monoclonal antibody DCS-6. Expression in tumor cells was compared with expression of cyclin D1 in endothelial cells and fibroblasts. An exclusively nuclear staining pattern was observed. Moreover, expression was directly compared with the expression observed by immunoblot analysis with the same antibody, as well as with mRNA expression and with the occurrence of genomic rearrangements within the BCL-1 locus. Of 13 MCL that were analyzed by immunohistochemistry and immunoblot, 12 showed overexpression with both techniques, whereas no overexpression was observed in 39 other NHL. Of 13 additional MCL studied either by immunohistochemistry or immunoblot, 11 also showed overexpression. Two lymphomas morphologically indistinguishable from MCL but with an aberrant immunophenotype (CD5 negative, CD10 positive) both lacked overexpression of cyclin D1. These results underscore the significance of overexpression of the cyclin D1 protein as a specific marker for MCL. Detection of cyclin D1 overexpression on formalin-fixed, paraffin-embedded tissues using the DCS-6 monoclonal antibody can be applied for routine diagnostic purposes.

A Multi-Target Drug Designing for BTK, MMP9, Proteasome And TAK1 for the clinical treatment of Mantle Cell Lymphoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Shahrukh Qureshi ◽  
Ravina Khandelwal ◽  
Maddala Madhavi ◽  
Naveesha Khurana ◽  
Neha Gupta ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Binding Capacity ◽  
D1 Protein ◽  
Chromosomal Translocation ◽  
Non Hodgkin Lymphoma ◽  
Target Drug ◽  
Pubchem Compound ◽  
Mantle Cell ◽  
Protein Receptors

Background: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal translocation t(11;14)(q13:q32). Aim: The Present study aims to identify a potential inhibition of MMP9, Proteasome, BTK, and TAK1 and also determine the most suitable and effective protein target for the MCL. Methodology: 9 known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1 were screened. SB-3CT (PubChem ID: 9883002), Oprozomib (PubChem ID: 25067547), Zanubrutinib (PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened compounds were obtained after the similarity search with compound (PubChem ID:102173753), PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual screened compounds. Results : MMP9 inhibitors shows the commendable affinity and good interaction profile of compound holding PubChem ID:102173753 over the most effective established inhibitor SB3CT. The pharmacophore study of the best virtual screened compound reveals the high efficacy of compound based on various interactions. The better affinity of the virtual screened compound with the target MMP9 protein was deduced using toxicity and integration profile studies. Conclusion: On the basis of ADMET profile, compound (PubChem ID: 102173753) could be a potent drug for MCL treatment. Similar to the established SB-3CT, the compound was also found to be non-toxic with LD50 values for both the compounds lying in the same range.

scholarly journals Suberoylanilide hydroxamic acid (SAHA; vorinostat) suppresses translation of cyclin D1 in mantle cell lymphoma cells

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2667-2673 ◽  
Author(s):  
Norihiko Kawamata ◽  
John Chen ◽  
H. Phillip Koeffler
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Hydroxamic Acid ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Kinase Assay ◽  
Suberoylanilide Hydroxamic Acid ◽  
Mrna Levels ◽  
Cyclin D1 Protein ◽  
Mantle Cell

Mantle cell lymphoma (MCL) has a chromosomal translocation resulting in the expression of the cyclin D1 gene driven by the powerful enhancer of the immunoglobulin heavy chain gene, leading to uncontrolled, overexpressed cyclin D1 protein. We showed that suberoylanilide hydroxamic acid (SAHA; vorinostat), one of the histone deacetylase inhibitors derived from hydroxamic acid, caused a dramatic decrease (90%) in protein levels of cyclin D1 after 8-hour exposure to SAHA (5 μM) in MCL lines (SP49, SP53, Jeko1). mRNA levels and protein stability of cyclin D1 were minimally affected by SAHA over 8 hours. In contrast, metabolic labeling assays showed that SAHA decreased incorporation of [35S]methionine into cyclin D1 protein. The drug also decreased levels of phosphorylated Akt, mammalian target of Rapamycin (mTOR), and eukaryotic translation initiation factor 4E binding protein (eIF4E-BP) and lowered the cap site binding activity of eIF4E in the MCL cells. In vitro phosphatidyl inositol (PI) kinase assay demonstrated that SAHA directly inhibited kinase activity of PI 3′ kinase. Taken together, SAHA caused a rapid decrease of cyclin D1 in MCL by blocking the translation of cyclin D1 by inhibiting the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR/eIF4E-BP pathway, probably by PI3K inhibition.

scholarly journals Cyclin D1 protein expression in mantle cell lymphoma

1995 ◽  
Vol 6 (6) ◽  
pp. 567-570 ◽  
Author(s):  
S. Alkan ◽  
B. Schnitzer ◽  
J.L. Thompson ◽  
L.C. Moscinski ◽  
C.W. Ross
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Cyclin D1 Protein ◽  
Mantle Cell

bcl-1 REARRANGEMENT AND CYCLIN D1 PROTEIN EXPRESSION IN MANTLE CELL LYMPHOMA

1996 ◽  
Vol 179 (3) ◽  
pp. 238-242 ◽  
Author(s):  
M. MICHAELA OTT ◽  
ANITA HELBING ◽  
GERMAN OTT ◽  
JIRI BARTEK ◽  
LARS FISCHER ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Cyclin D1 Protein ◽  
Mantle Cell

scholarly journals Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma

Blood ◽  
1995 ◽  
Vol 86 (7) ◽  
pp. 2715-2723 ◽  
Author(s):  
CJ de Boer ◽  
E Schuuring ◽  
E Dreef ◽  
G Peters ◽  
J Bartek ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
D1 Protein ◽  
Formalin Fixed Paraffin ◽  
Cyclin D1 Protein ◽  
Mantle Cell ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Mantle cell lymphoma (MCL) is a clinicopathologic entity that is difficult to diagnose on histopathologic criteria. Approximately 50% to 70% of MCL contain a t(11;14)(q13;q32) translocation involving the cyclin D1 gene. Irrespective of this rearrangement, almost all MCL show overexpression of the cyclin D1 gene at the mRNA level. Other B-cell non-Hodgkin's lymphomas (NHL) do not show this rearrangement or overexpression of cyclin D1. We developed an immunohistochemical assay to detect overexpression of the cyclin D1 protein on conventional formalin-fixed, paraffin-embedded biopsies using the well-defined monoclonal antibody DCS-6. Expression in tumor cells was compared with expression of cyclin D1 in endothelial cells and fibroblasts. An exclusively nuclear staining pattern was observed. Moreover, expression was directly compared with the expression observed by immunoblot analysis with the same antibody, as well as with mRNA expression and with the occurrence of genomic rearrangements within the BCL-1 locus. Of 13 MCL that were analyzed by immunohistochemistry and immunoblot, 12 showed overexpression with both techniques, whereas no overexpression was observed in 39 other NHL. Of 13 additional MCL studied either by immunohistochemistry or immunoblot, 11 also showed overexpression. Two lymphomas morphologically indistinguishable from MCL but with an aberrant immunophenotype (CD5 negative, CD10 positive) both lacked overexpression of cyclin D1. These results underscore the significance of overexpression of the cyclin D1 protein as a specific marker for MCL. Detection of cyclin D1 overexpression on formalin-fixed, paraffin-embedded tissues using the DCS-6 monoclonal antibody can be applied for routine diagnostic purposes.

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