Human MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells
| العنوان: | Human MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells |
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| المؤلفون: | Ruben D. Carrasco, Vignesh Shanmugam, Maria Demos, Maria Luisa Guerrera, Steven P. Treon, Audrey Dalgarno, Neil A. Patel, Amanda Kofides, Kyle Wright, Guang Yang, Helen Tanton, Tomasz Sewastianik, Meng Jiang, Zachary R. Hunter, Geraldine S. Pinkus, Petr Jarolim, Anwesha Nag, Peter S. Dennis, Nikhil C. Munshi, Ying Huang, Keith Adler |
| المصدر: | Blood Advances. 3:3360-3374 |
| بيانات النشر: | American Society of Hematology, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Biopsy, Gene Expression, Mice, Transgenic, Biology, Immunophenotyping, Malignant transformation, Lymphoplasmacytic Lymphoma, Mice, immune system diseases, hemic and lymphatic diseases, Biomarkers, Tumor, medicine, Animals, Humans, Genetic Predisposition to Disease, Neoplastic transformation, Alleles, Genetic Association Studies, B-Lymphocytes, Lymphoid Neoplasia, Waldenstrom macroglobulinemia, Hematology, medicine.disease, Immunohistochemistry, Lymphoma, Disease Models, Animal, Cell Transformation, Neoplastic, medicine.anatomical_structure, Amino Acid Substitution, Immunoglobulin M, Mutation, Myeloid Differentiation Factor 88, Cancer research, biology.protein, Bone marrow, Neoplasm Grading, Waldenstrom Macroglobulinemia, Transcriptome, Diffuse large B-cell lymphoma |
| الوصف: | MYD88 L265P is the most common mutation in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and one of the most frequent in poor-prognosis subtypes of diffuse large B-cell lymphoma (DLBCL). Although inhibition of the mutated MYD88 pathway has an adverse impact on LPL/WM and DLBCL cell survival, its role in lymphoma initiation remains to be clarified. We show that in mice, human MYD88L265P promotes development of a non-clonal, low-grade B-cell lymphoproliferative disorder with several clinicopathologic features that resemble human LPL/WM, including expansion of lymphoplasmacytoid cells, increased serum immunoglobulin M (IgM) concentration, rouleaux formation, increased number of mast cells in the bone marrow, and proinflammatory signaling that progresses sporadically to clonal, high-grade DLBCL. Murine findings regarding differences in the pattern of MYD88 staining and immune infiltrates in the bone marrows of MYD88 wild-type (MYD88WT) and MYD88L265P mice are recapitulated in the human setting, which provides insight into LPL/WM pathogenesis. Furthermore, histologic transformation to DLBCL is associated with acquisition of secondary genetic lesions frequently seen in de novo human DLBCL as well as LPL/WM-transformed cases. These findings indicate that, although the MYD88L265P mutation might be indispensable for the LPL/WM phenotype, it is insufficient by itself to drive malignant transformation in B cells and relies on other, potentially targetable cooperating genetic events for full development of lymphoma. |
| تدمد: | 2473-9537 2473-9529 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb02bd334fed7de86d259f6fb8cc4fd2 https://doi.org/10.1182/bloodadvances.2019000588 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eb02bd334fed7de86d259f6fb8cc4fd2 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 24739537 24739529 |
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