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BIOMARKER:

Chr t(11;14)(q13;q32)

7d
Enrollment open
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TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • FAT1 (FAT atypical cadherin 1) • POT1 (Protection of telomeres 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
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CD20 positive • Chr t(11;14) • KMT2D mutation • BIRC3 mutation • CCND1 overexpression • SMARCA4 mutation • Chr t(11;14)(q13;q32) • MYC positive
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Rituxan (rituximab) • cyclophosphamide • Calquence (acalabrutinib) • Tecartus (brexucabtagene autoleucel) • fludarabine IV
28d
CARAMEL: Acalabrutinib and Rituximab in Previously Untreated Mantle Cell Lymphoma (clinicaltrials.gov)
P2, N=26, Not yet recruiting, University College, London | Trial completion date: Aug 2023 --> May 2026 | Trial primary completion date: Aug 2023 --> May 2026
Trial completion date • Trial primary completion date
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CCND1 (Cyclin D1)
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Chr t(11;14) • CCND1 overexpression • Chr t(11;14)(q13;q32)
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Rituxan (rituximab) • Calquence (acalabrutinib)
28d
Dual Expression of Immunoglobulin Light Chains in Plasma Cell Myeloma: A Case Report and Literature Review. (PubMed, Appl Immunohistochem Mol Morphol)
IHC results in myeloma with dual expression of Ig light chains may suggest polyclonal plasma cell population, especially when plasma cells do not form sheets in the bone marrow. In an appropriate clinical setting, other investigations are needed to exclude plasma cell neoplasm, even with seemingly "polytypic" results by IHC.
Review • Journal
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KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • NCAM1 (Neural cell adhesion molecule 1)
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Chr t(11;14) • CCND1 expression • Chr t(11;14)(q13;q32)
1m
A t(11;14)(q13;q32)/CCND1::IGH carrying progenitor germinal B-cell with subsequent cytogenetic aberrations contributes to the development of classic Hodgkin lymphoma. (PubMed, Cancer Genet)
We also analyzed recurrent cytogenetic aberrations in t(11;14) positive mantle cell lymphoma (MCL) and those found in cHL from the literature to assess genetic overlap, clonal evolution, and to identify potential signaling pathways in cHL with CCND1::IGH. This analysis suggests the development of t(11;14)+ cHL and MCL from a transformed precursor cell with t(11;14) through genetic evolution and consequent deregulated pathways, including the NF-κB and NOTCH1 signaling.
Journal
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NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • PAX5 (Paired Box 5)
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Chr t(11;14) • CCND1 expression • Chr t(11;14)(q13;q32)
2ms
Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma (clinicaltrials.gov)
P2, N=27, Suspended, City of Hope Medical Center | Trial completion date: Mar 2023 --> Sep 2023 | Trial primary completion date: Sep 2022 --> Sep 2023
Trial completion date • Trial primary completion date • Combination therapy
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CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1)
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Chr t(11;14) • CCND1 overexpression • Chr t(11;14)(q13;q32)
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Calquence (acalabrutinib) • Ukoniq (umbralisib) • Utuxin (ublituximab)
2ms
Allogenic CD19-targeting CAR-γδT Cell Therapy in r/r NHL (clinicaltrials.gov)
P1/2, N=30, Recruiting, Chinese PLA General Hospital
New P1/2 trial
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BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • CD19 (CD19 Molecule) • BCL6 (B-cell CLL/lymphoma 6) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • IL10 (Interleukin 10)
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Chr t(11;14) • CD19 positive • CCND1 overexpression • BCL6 rearrangement • Chr t(11;14)(q13;q32) • BCL2 rearrangement • CD20 negative
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cyclophosphamide • fludarabine IV
3ms
New P2 trial
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TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • NOTCH2 (Notch 2) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
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TP53 mutation • Chr del(17p) • CD20 positive • Chr t(11;14) • CDKN2A mutation • CCND1 overexpression • Chr t(11;14)(q13;q32) • MYC positive • BCL2 amplification
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Venclexta (venetoclax) • pirtobrutinib (LOXO-305)
3ms
Enrollment change
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TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • FAT1 (FAT atypical cadherin 1) • POT1 (Protection of telomeres 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
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CD20 positive • Chr t(11;14) • KMT2D mutation • BIRC3 mutation • CCND1 overexpression • SMARCA4 mutation • Chr t(11;14)(q13;q32) • MYC positive
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Rituxan (rituximab) • cyclophosphamide • Calquence (acalabrutinib) • Tecartus (brexucabtagene autoleucel) • fludarabine IV
3ms
Acalabrutinib for the Treatment of Ibrutinib-Intolerant Mantle Cell Lymphoma (clinicaltrials.gov)
P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023
Trial completion date • Trial primary completion date
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CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1)
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CD20 positive • Chr t(11;14) • CCND1 overexpression • Chr t(11;14)(q13;q32)
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ibrutinib • Calquence (acalabrutinib)
4ms
New P1 trial
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TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • FAT1 (FAT atypical cadherin 1) • POT1 (Protection of telomeres 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
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CD20 positive • Chr t(11;14) • KMT2D mutation • BIRC3 mutation • CCND1 overexpression • SMARCA4 mutation • Chr t(11;14)(q13;q32) • MYC positive
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Rituxan (rituximab) • cyclophosphamide • Calquence (acalabrutinib) • Tecartus (brexucabtagene autoleucel) • fludarabine IV
4ms
A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma (clinicaltrials.gov)
P1/2, N=50, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting | Initiation date: Feb 2022 --> Jul 2022
Enrollment open • Trial initiation date • Combination therapy
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CCND1 (Cyclin D1)
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Chr t(11;14) • CCND1 overexpression • Chr t(11;14)(q13;q32)
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AZD0466
7ms
PROGNOSTIC ROLE OF GENETIC ABNORMALITIES IN MANTLE CELL LYMPHOMA (EHA 2022)
It was also shown that in the group of patients with changes in the C-MYC gene, additional genetic anomalies were more often detected, which are an unfavorable prognostic factor: a complex karyotype (the presence of three or more aberrations) – 37,5% and 16,9%, and aberrations involving the gene TP53 – 50,0% and 16,9%. Changes in these genes are associated with shorter progression-free survival rates.
TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1)
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Chr t(11;14) • TP53 deletion • MYC rearrangement • Chr t(11;14)(q13;q32)
7ms
Deep Neural Networks and Machine Learning Radiomics Modelling for Prediction of Relapse in Mantle Cell Lymphoma. (PubMed, Cancers (Basel))
Our optimised CNN developed by ourselves correctly predicted MCL relapse in 70% of the patients on baseline CT imaging. Once prospectively tested in clinical trials with a larger sample size, our proposed 3D deep learning model could facilitate clinical management by precision imaging in MCL.
Journal
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CCND1 (Cyclin D1)
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Chr t(11;14) • CCND1 overexpression • Chr t(11;14)(q13;q32)
9ms
Establishment and characterization of a new mantle cell lymphoma cell line with a NOTCH2 mutation, ArBo (AACR 2022)
Additionally, a dose dependent decrease in the expression of CD23 was observed by flow cytometry following treatment with gliotoxin.To determine the dependence of Arbo on B-cell receptor (BCR) signaling for survival, we cultured the cells with increasing concentrations of the BTK inhibitor ibrutinib for 48h. Inhibition of cell growth was observed in a dose-dependent manner resulting in an IC50 of 0.4 µM.In conclusion, Arbo is a novel blastoid MCL cell line with a NOTCH2 mutation that is fully characterized and will be made available to the research community.Supported by a grant from the Ladies Leukemia League, Inc., of the Gulf South Region.
Preclinical • IO biomarker
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TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • CD38 (CD38 Molecule) • NOTCH2 (Notch 2) • CD5 (CD5 Molecule) • FCER2 (Fc Fragment Of IgE Receptor II)
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TP53 mutation • ATM mutation • Chr t(11;14) • Chr t(11;14)(q13;q32) • NOTCH2 mutation • CD5 positive
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ibrutinib
12ms
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With Secondary Acquisition of t(11;14)(q13;q32)/CCND1-IGH: A Rare Variant Of Richter Transformation to Mantle Cell Lymphoma. (PubMed, Clin Lymphoma Myeloma Leuk)
The retention of immunophenotype suggests a clonal relationship between CLL/SLL and mantle cell lymphoma. While the acquisition of t(11;14)(q13;q32); CCND1-IGH likely alters the disease course, the pathogenesis of this illegitimate translocation in CLL remains to be studied.
Journal
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CCND1 (Cyclin D1)
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Chr t(11;14) • CCND1 expression • Chr t(11;14)(q13;q32)
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Rituxan (rituximab) • Leukeran (chlorambucil) • fludarabine IV
1year
[VIRTUAL] Impact of Cytogenetic Aberrations on Clinical Characteristics and Treatment Response in Indian Multiple Myeloma Patients: A Single Tertiary Center Experience (AMP 2021)
This study aimed to evaluate the association between cytogenetic abnormalities and clinicohaematological characteristics at diagnosis, and retrospectively compare the overall response rate to 2 triple drug combinations comprised of bortezomib, cyclophosphamide, and dexamethasone (VCd) versus thalidomide, cyclophosphamide, and dexamethasone (VRd) in transplant eligible patients with untreated MM. The key differences in baseline characteristics at presentation compared to Western population could be attributed to ethnic diversity. Triplet induction therapy VRd was superior as regards to response rates compared to VCd arm.
Clinical
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TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • CCND1 (Cyclin D1) • B2M (Beta-2-microglobulin)
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Chr t(11;14) • TP53 deletion • Chr t(4;14) • Chr t(14;16) • Chr t(11;14)(q13;q32) • IGH translocation • Chr t(14;20)
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bortezomib • thalidomide
1year
Mantle Cell Lymphoma with Chronic Lymphocytic Leukemia-Like Features: A Diagnostic Mimic and Pitfall. (PubMed, Hum Pathol)
They may pose a diagnostic challenge. However, patients with CLL-like MCL also have distinctive immunophenotypic features that are useful to distinguish these neoplasms from CLL.
Journal
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CCND1 (Cyclin D1) • IGH (Immunoglobulin Heavy Locus) • CD200 (CD200 Molecule) • SOX11 (SRY-Box Transcription Factor 11) • FCER2 (Fc Fragment Of IgE Receptor II)
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Chr t(11;14) • CD20 expression • CCND1 overexpression • Chr t(11;14)(q13;q32) • CD200 expression • SOX11 expression
1year
Detection of CCND1 Overexpression By RNA-Seq from Tna Samples As a Surrogate for t(11:14) Translocation Traditionally Measured By FISH in Multiple Myeloma Patients for Improved Patient Care (ASH 2021)
In this study we evaluated our existing NGS assay for CCND1 overexpression using TNA as a surrogate for traditional FISH, while demonstrating the accuracy of the RNA quantitation by NGS using qRT-PCR. We developed an RNA-seq based CCND1 expression assay that could be used to complement traditional FISH testing especially if there is limited specimen. The confirmation of overexpression in FISH negative samples may suggest new ways to improve MM patients risk stratification and treatment.
Clinical
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CCND1 (Cyclin D1) • IGH (Immunoglobulin Heavy Locus) • SDC1 (Syndecan 1) • RPL5 (Ribosomal Protein L5)
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Chr t(11;14) • CCND1 overexpression • CCND1 expression • Chr t(11;14)(q13;q32) • CCND1-H