Objective: In patients with large B-cell lymphoma (LBCL) according to WHO, the prognostic significance of MYC translocation is still not sufficiently clarified. We therefore aimed to investigate whether prognostication could be improved in patients with MYC translocation positive LBCL by additional stratification according to MYC and BCL2 protein expression levels or MYC translocation partner gene as well as concurrent BCL2 and/or BCL6 translocation (DH).
Methods: From an unselected consecutive cohort of >600 patients with LBCL investigated with fluorescent in situ hybridization (FISH), 64 patients were diagnosed with MYC translocation positive LBCL and included in the study. They were further investigated for supplemental translocations with FISH and MYC and BCL2 protein expression with immunohistochemistry (IHC).
Results: MYC expression >75% was associated with both reduced progression-free survival (PFS) and overall survival (OS) (PFS: HR 6.8 (95% CI 1.5-31), P = 0.004. OS: HR 4.3 (95% CI 0.9-21), P = 0.05). Immunoglobulin (IG) MYC translocation partner gene was related to high MYC protein expression (P = 0.047) but was not prognostic for PFS (P = 0.8) or OS (P = 0.6). DH did not confer a worse outcome compared to MYC single hit (SH). These findings were confirmed in a comparable, independent validation cohort of 28 patients with MYC translocation positive LBCL. All patients included in the survival analyses were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOEP (R-CHOP + etoposide).
Conclusion: These findings suggest that in patients with LBCL stratification by MYC protein expression level significantly improves the prognostic impact associated with MYC translocation.
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http://dx.doi.org/10.1111/ejh.13219 | DOI Listing |
Adv Biomed Res
November 2024
Department of Cellular and Molecular Nutrition, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background: Acquisition of stem-like properties requires overcoming the epigenetic barrier of differentiation and re-expression of several genes involved in stemness and the cell cycle. DNA methylation is the classic epigenetic mechanism for de/differentiation. The writers and erasers of DNA methylation are not site-specific enzymes for altering specific gene methylation.
View Article and Find Full Text PDFClin Epigenetics
December 2024
Univ. Grenoble Alpes, Inserm, CNRS, Institute for Advanced Biosciences, Grenoble, France.
Background: MYC-driven lymphomas are a subset of B-cell lymphomas characterized by genetic alterations that dysregulate the expression of the MYC oncogene. When overexpressed, typically through chromosomal translocations, amplifications, or other mechanisms, MYC can drive uncontrolled cell growth and contribute to cancer development. MYC-driven lymphomas are described as aggressive entities which require intensive treatment approaches and can be associated with poor prognosis.
View Article and Find Full Text PDFAnn Hematol
December 2024
Department of Hematology, Tohoku University Hospital, Sendai, Japan.
Although rearrangement of the MYC oncogene (MYC-R) is frequently observed in aggressive B-cell lymphomas, it is extremely rare in T-cell malignancies. A 64-year-old man who had been under observation for several years because of asymptomatic pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) was admitted to our hospital because of poor general condition and hypotension. Blood tests revealed thrombocytopenia and elevated serum lactate dehydrogenase levels, whereas computed tomography revealed systemic lymphadenopathy and splenomegaly.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Intracellular Signaling and Transport, Institute of Cytology, Russian Academy of Sciences, Tikhoretskii pr. 4, St. Petersburg 194064, Russia.
Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for biomedical applications, such as cell therapy, disease modeling, and drug screening. At the same time, long-term cultivation, which is necessary to prepare a sufficient amount of cellular material for therapeutic and research purposes, is accompanied by the development of replicative senescence. Partial reprogramming emerged as a novel method that shows promising results in the rejuvenation of cells in vitro and in vivo; however, it has not yet been applied for human MSCs that have undergone replicative senescence in culture.
View Article and Find Full Text PDFHum Pathol
December 2024
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:
Burkitt lymphoma is a mature aggressive B-cell neoplasm with distinctive clinical and morphologic features, a germinal center B-cell immunophenotype, a high proliferation index and MYC rearrangement with an immunoglobulin gene partner. Initially described in equatorial Africa by a surgeon, Denis Burkitt, African (endemic) Burkitt lymphoma was the first neoplasm shown to be associated with a virus, Epstein-Barr virus (EBV), and the first neoplasm shown to be associated with a chromosomal translocation, IGH::MYC. In this article, we provide a brief historical introduction of Burkitt lymphoma, followed by a review of all aspects of this neoplasm including pathogenesis, clinical presentation, morphology, immunophenotype, cytogenetics and molecular findings.
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