Browsing by Subject "Clonal evolution"

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    Multiple Myeloma Insights from Single-Cell Analysis: Clonal Evolution, the Microenvironment, Therapy Evasion, and Clinical Implications
    (MDPI, 2025-02-14) Li, Sihong; Liu, Jiahui; Peyton, Madeline; Lazaro, Olivia; McCabe, Sean D.; Huang, Xiaoqing; Liu, Yunlong; Shi, Zanyu; Zhang, Zhiqi; Walker, Brian A.; Johnson, Travis S.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Multiple myeloma (MM) is a complex and heterogeneous hematologic malignancy characterized by clonal evolution, genetic instability, and interactions with a supportive tumor microenvironment. These factors contribute to treatment resistance, disease progression, and significant variability in clinical outcomes among patients. This review explores the mechanisms underlying MM progression, including the genetic and epigenetic changes that drive clonal evolution, the role of the bone marrow microenvironment in supporting tumor growth and immune evasion, and the impact of genomic instability. We highlight the critical insights gained from single-cell technologies, such as single-cell transcriptomics, genomics, and multiomics, which have enabled a detailed understanding of MM heterogeneity at the cellular level, facilitating the identification of rare cell populations and mechanisms of drug resistance. Despite the promise of advanced technologies, MM remains an incurable disease and challenges remain in their clinical application, including high costs, data complexity, and the need for standardized bioinformatics and ethical considerations. This review emphasizes the importance of continued research and collaboration to address these challenges, ultimately aiming to enhance personalized treatment strategies and improve patient outcomes in MM.
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    Progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma and B-cell prolymphocytic leukemia: Report from the 2021 SH/EAHP Workshop
    (Oxford University Press, 2023) Czader, Magdalena; Amador, Catalina; Cook, James R.; Thakkar, Devang; Parker, Clay; Dave, Sandeep S.; Dogan, Ahmet; Duffield, Amy S.; Nejati, Reza; Ott, German; Xiao, Wenbin; Wasik, Mariusz; Goodlad, John R.; Pathology and Laboratory Medicine, School of Medicine
    Objectives: Session 3 of the 2021 Workshop of the Society for Hematopathology/European Association for Haematopathology examined progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and B-cell prolymphocytic leukemia (B-PLL). Methods: Thirty-one cases were reviewed by the panel. Additional studies such as immunohistochemistry and molecular genetic testing, including whole-exome sequencing and expression profiling, were performed in select cases. Results: Session 3 included 27 CLL/SLL cases and miscellaneous associated proliferations, 3 cases of B-PLL, and 1 case of small B-cell lymphoma. The criteria for -accelerated CLL/SLL are established for lymph nodes, but extranodal disease can be diagnostically challenging. Richter transformation (RT) is a broad term and includes true transformation from original CLL/SLL clone(s) and clonally unrelated neoplasms. The morphologic, immunophenotypic, and genetic spectrum is diverse with classical and highly unusual examples. T-cell proliferations can also be encountered in CLL/SLL. B-cell prolymphocytic leukemia is a rare, diagnostically challenging disease due to its overlaps with other lymphoid neoplasms. Conclusions: The workshop highlighted complexity of progression and transformation in CLL/SLL and B-PLL, as well as diagnostic caveats accompanying heterogeneous presentations of RT and other manifestations of disease progression. Molecular genetic studies are pivotal for diagnosis and determination of clonal relationship, and to predict response to treatment and identify resistance to targeted therapy.