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Chronic Lymphocytic Leukemia: Molecular Pathologies and Therapeutic Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 January 2026 | Viewed by 2156

Special Issue Editor


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Guest Editor
Department of Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33315, Taiwan
Interests: leukemia; hematopoietic cell transplantation; mesenchymal stem cells; immunotherapy

Special Issue Information

Dear Colleagues,

Understanding the genomic landscapes of different subtypes of Chronic Lymphocytic Leukemia (CLL) is crucial for improving treatment, identifying predictive indicators, understanding resistance mechanisms, conducting clinical trials, and developing biomarkers. This knowledge helps develop personalized therapies, predict disease progression, and develop strategies to address or prevent resistance to therapies. A deep understanding of the genomic landscape is essential for precision medicine, patient outcomes, and innovative research.

This Special Issue focuses on recent studies that aim to highlight the latest research on the genomic landscapes in CLL. These studies should provide valuable insights that have paved the way for targeted therapies, personalized treatment plans, risk stratification, continuous disease progression monitoring, clinical trials, and biomarker development. These insights allow for the creation of drugs that can target specific genetic mutations, improving treatment effectiveness and reducing side effects. Genomic profiling is also helpful in monitoring disease progression, allowing for timely adjustments in treatment. In general, genomic knowledge greatly improves personalized treatment strategies for patients with CLL.

Dr. Tang Her Jaing
Guest Editor

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Keywords

  • chronic lymphocytic leukemia
  • genomic landscapes
  • precision medicine
  • clinical trials
  • biomarker

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Published Papers (1 paper)

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Review

23 pages, 1508 KB  
Review
Richter Transformation in Chronic Lymphocytic Leukemia: Current Treatment Challenges and Evolving Therapies
by Zi-Chi Lin, Ming-Jen Chan, Tang-Her Jaing, Tung-Liang Lin, Yu-Shin Hung and Yi-Jiun Su
Int. J. Mol. Sci. 2025, 26(17), 8747; https://doi.org/10.3390/ijms26178747 - 8 Sep 2025
Viewed by 1404
Abstract
Richter transformation (RT) affects 2–10% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma—most often diffuse large B-cell lymphoma—with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH1 mutations, stereotyped B-cell receptors, [...] Read more.
Richter transformation (RT) affects 2–10% of chronic lymphocytic leukemia (CLL) patients, evolving into an aggressive lymphoma—most often diffuse large B-cell lymphoma—with poor prognosis, especially when clonally related to CLL. Key risk factors include unmutated IGHV, TP53 and NOTCH1 mutations, stereotyped B-cell receptors, and complex cytogenetics. This review summarizes RT biology, clinical predictors, and treatment outcomes. Traditional chemoimmunotherapy (e.g., R-CHOP) yields complete response rates around 20–30% and median overall survival of 6–12 months; intensified regimens (R-EPOCH, hyper-CVAD) offer only modest gains. Allogeneic hematopoietic stem cell transplantation is potentially curative but limited to fit patients due to high treatment-related mortality. Emerging therapies now include Bruton’s tyrosine kinase and BCL-2 inhibitors, which achieve partial responses but short progression-free survival. CD19-directed chimeric antigen receptor T-cell therapies produce overall response rates of 60–65%, though relapses remain frequent. Bispecific antibodies (e.g., CD3×CD20 agents epcoritamab and mosunetuzumab) show promising activity and tolerable toxicity in relapsed/refractory RT. Ongoing trials are exploring combinations with checkpoint inhibitors, triplet regimens, and novel targets such as ROR1, CD47, and CDK9. Continued research into optimized induction, consolidation, and innovative immunotherapies is essential to improve outcomes in this biologically distinct, high-risk CLL-related lymphoma. Full article
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