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 A Rare Manifestation of a Rare Disease: Mantle Cell Lymphoma Presenting With Aseptic Meningitis

2019 ◽  
Vol 7 ◽  
pp. 232470961985864
Author(s):  
Elvira Umyarova ◽  
Sreedhar Adapa ◽  
Srikanth Naramala ◽  
Vijay Gayam ◽  
Narothama Reddy Aeddula ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Aseptic Meningitis ◽  
Cell Lymphoma ◽  
Chromosomal Translocation ◽  
Aberrant Expression ◽  
Non Hodgkin Lymphoma ◽  
Clonal Proliferation ◽  
Mantle Cell ◽  
Short Overall Survival ◽  
Apoptotic Pathways

Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin lymphoma characterized by clonal proliferation of follicular mantle zone B lymphocytes. It is caused by abnormal chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1. This leads to activation of anti-apoptotic pathways and abnormal proliferation of MCL cells. Patients can present with an indolent course or a fulminant disease with short overall survival. The disease frequently involves extranodal organs, but rarely manifests with neurological symptoms. We report a rare case of aberrant CD5-negative MCL presenting with aseptic meningitis.

scholarly journals Large-scale nuclear remodeling and transcriptional deregulation occur on both derivative chromosomes after Mantle Cell Lymphoma chromosomal translocation

2019 ◽  
Author(s):  
Fatimata Bintou Sall ◽  
Andrei Pichugin ◽  
Olga Iarovaia ◽  
Ana Barat ◽  
Tatyana Tsfasman ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Large Scale ◽  
Cell Lymphoma ◽  
Nuclear Periphery ◽  
Chromosomal Translocation ◽  
Non Hodgkin Lymphoma ◽  
Close Proximity ◽  
Mantle Cell ◽  
Balanced Translocations ◽  
Nuclear Remodeling

ABSTRACTRecurrent chromosomal translocations are found in many blood and solid cancers. Balanced translocations, frequent in lymphoid malignancies, lead to the formation of two aberrant derivative (der) chromosomes. This event often leads to overexpression of an oncogene. In many cases, the expression of an oncogene is not enough to produce a malignant phenotype; however, most part of the studies focus on the events involving the chromosome where the oncogene is located, but rarely the other der chromosome where other oncogenic alterations may potentially arise. Mantle cell lymphoma (MCL), an aggressive B-cell non-Hodgkin lymphoma, is a perfect example of this. In 85% of the cases, it is characterized by the translocation t(11;14), which leads to the overexpression of cyclin D1 (CCND1) gene which results juxtaposed to the immunoglobulin heavy chain (IGH) gene on the der14 chromosome. This feature alone is not sufficient to induce oncogenesis. Here we focused on the der11 chromosome. We demonstrated that expression of 88 genes located in a 15mb region close to the translocation breakpoint on the der11 was deregulated both in the GRANTA-519 MCL cell line and in B-cells from MCL patients. We found that a large segment of der11containing deregulated genes was relocated from its normal position in the nuclear periphery towards the center of the nucleus in close proximity to the nucleolus where the abundant nucleolar protein nucleolin binds a subset of genes located close to the breakpoint and activates their expression. This finding allowed to identify new potential oncogenes involved in MCL and the mechanisms of their upregulation.

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 Mantle Cell Lymphoma Mimicking Rectal Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Engin Kelkitli ◽  
Hilmi Atay ◽  
Levent Yıldız ◽  
Ahmet Bektaş ◽  
Mehmet Turgut
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Rectal Carcinoma ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Extranodal Involvement ◽  
Non Hodgkin Lymphoma ◽  
Rectal Involvement ◽  
Mantle Cell ◽  
Rectal Mass

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma. After the (11;14) translocation was identified as its constant finding in 1992, MCL was recognized as a separate subgroup of non-Hodgkin lymphoma (NHL). In MCL, extranodal involvement may be observed in the bone marrow, the spleen, the liver, and the gastrointestinal system (GIS). Cases of MCL that present with a massive and solitary rectal mass are rare in the literature. In this case report, our aim was to present an MCL patient with a rarely observed solitary rectal involvement mimicking rectal carcinoma and to discuss treatment options for this patient.

scholarly journals An open‐label phase 2 trial of entospletinib in indolent non‐Hodgkin lymphoma and mantle cell lymphoma

2018 ◽  
Vol 184 (2) ◽  
pp. 215-222 ◽  
Author(s):  
David J. Andorsky ◽  
Kathryn S. Kolibaba ◽  
Sarit Assouline ◽  
Andres Forero‐Torres ◽  
Vicky Jones ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Phase 2 ◽  
Open Label ◽  
Non Hodgkin Lymphoma ◽  
Phase 2 Trial ◽  
Mantle Cell ◽  
Open Label Phase

scholarly journals Mantle Cell Lymphoma Presenting as a Subcutaneous Mass of the Right Leg

2020 ◽  
Vol 13 (2) ◽  
pp. 774-782
Author(s):  
Drew A. Fajardo ◽  
Joel France ◽  
Bogna I. Targonska ◽  
H. Bobby Kahlon ◽  
Max J. Coppes
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell ◽  
History Of ◽  
Subcutaneous Mass ◽  
Systemic Symptoms ◽  
The Right

Mantle cell lymphoma (MCL) is a relatively rare B-cell non-Hodgkin lymphoma, typically presenting with extensive lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal sites can also be involved. We discuss a 73-year-old man whose MCL presented with a 6-month history of a subdermal mass of the right upper thigh and no systemic symptoms.

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

Complex analysis of cyclin D1 expression in mantle cell lymphoma: two cyclin D1-negative cases detected

2009 ◽  
Vol 62 (10) ◽  
pp. 948-950 ◽  
Author(s):  
L Stefancikova ◽  
M Moulis ◽  
P Fabian ◽  
I Falkova ◽  
I Vasova ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Complex Analysis ◽  
Cell Lymphoma ◽  
In Situ Hybridisation ◽  
D1 Protein ◽  
Fluorescence In Situ Hybridisation ◽  
Cyclin D2 ◽  
Mantle Cell ◽  
High Level

Background and Aim:The cytogenetic and diagnostic hallmark of mantle cell lymphoma (MCL) is translocation t(11;14)(q13;q32), resulting in overexpression of cyclin D1. Cyclin D1 expression was analysed in 32 cases of MCL.Methods:The t(11;14) translocation was detected by fluorescence in situ hybridisation, level of cyclin D1 mRNA by competitive RT-PCR, and level of cyclin D1 and D2 proteins by immunohistochemistry and/or immunoblotting.Results:In 30 cases, the presence of translocation t(11;14), a high level of cyclin D1 mRNA, and a high level of the cyclin D1 protein were confirmed. Two cyclin D1-negative cases overexpressing cyclin D2 were detected by immunoblotting.Conclusions:There are rare cyclin D1-negative cases of MCL overexpressing cyclin D2. Anti-cyclin D1 antibodies with low specificity can bind both cyclin D1 and cyclin D2, thus providing false cyclin D1-positive signals in immunohistochemical analysis.

Sign in / Sign up

Export Citation Format

Share Document