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Cancers
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Chronic Lymphocytic Leukemia: Identification of Novel Prognostic Markers and Their...
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Chronic Lymphocytic Leukemia: Identification of Novel Prognostic Markers and Their Clinical Application

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (10 June 2024) | Viewed by 3736

Special Issue Editor

Prof. Dr. Lynne V. Abruzzo

E-Mail Website
Guest Editor
Department of Pathology, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA
Interests: hematopathology; lymphoid leukemias and lymphomas; cytogenetics; molecular diagnostics

Special Issue Information

Dear Colleagues,

Chronic lymphocytic leukemia (CLL), the most common leukemia in the Western Hemisphere, is characterized by the accumulation of malignant, mature-appearing B-lymphocytes in blood, bone marrow, and lymph nodes. The disease course is highly variable; some patients develop rapidly progressive disease, while others have an indolent course that spans decades. Identification of novel prognostic markers and their clinical application is an important area of research in CLL. Prognostic markers are used to predict the disease course and the likelihood of response to treatment. In recent years, significant progress has been made in identifying and implementing new prognostic markers. These include immunophenotypic and molecular genetic markers, including recurrent chromosomal abnormalities, gene mutations, and epigenetic alterations. This research has enhanced our understanding of the disease’s pathogenesis and our ability to predict the prognosis of individual patients. Ultimately, the identification of new prognostic markers will help to guide treatment decisions and improve outcomes for patients with CLL.

Prof. Dr. Lynne V. Abruzzo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chronic lymphocytic leukemia (CLL)
  • prognostic markers
  • clinical application
  • response
  • treatment

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Published Papers (2 papers)

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Research

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10 pages, 1787 KiB  
Article
Beta-2-Microglobulin Maintains Overall Survival Prediction in Binet A Stage Chronic Lymphocytic Leukemia Patients with Compromised Kidney Function in Both Treatment Eras of Chemoimmunotherapy and Targeted Agents
by Jan-Paul Bohn, Valentina Stolzlechner, Georg Göbel, Wolfgang Willenbacher, Markus Pirklbauer, Normann Steiner and Dominik Wolf
Cancers 2024, 16(22), 3744; https://doi.org/10.3390/cancers16223744 - 6 Nov 2024
Viewed by 1372
Abstract
Background: Elevated beta-2-microglobulin (B2M) plasma levels commonly imply a higher CLL-IPI risk category for short overall survival (OS), but the risk model was not adjusted for compromised kidney function and not validated in Binet A stage CLL patients. Methods: CLL patients [...] Read more.
Background: Elevated beta-2-microglobulin (B2M) plasma levels commonly imply a higher CLL-IPI risk category for short overall survival (OS), but the risk model was not adjusted for compromised kidney function and not validated in Binet A stage CLL patients. Methods: CLL patients were identified from 2000 to 2022 at Innsbruck University Hospital, Austria. B2M levels, CLL-IPI risk stratification, and kidney function were assessed. Treatment modalities in case of disease progression and OS data during follow-up were evaluated. Results: A total of 259 Binet A stage CLL patients were identified; 16.9% (n = 44/259) presented with concurrent chronic kidney disease (CKD, GFR < 60 mL/min). Median OS was 170 months and was similar in CKD and non-CKD patients (p = 0.25). The CLL-IPI facilitated prognostic segregation in both CKD (p = 0.02) and non-CKD patients (p = 0.008). Although more frequently elevated in CKD patients (44.1% versus 10.6%, p < 0.001), B2M > 3.5 mg/L remained associated with inferior OS in this subgroup (p = 0.03). Contrary to the CLL-IPI, the prognostic value of B2M alone was also maintained in CLL patients diagnosed and potentially treated frontline in the era of targeted agents (2014–2022, p = 0.03). Conclusions: B2M retains its prognostic value for OS in early-stage CLL patients with concurrent CKD and still represents a promising covariate for up-coming prognostic models to identify patients at high risk for inferior OS in the era of targeted agents. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Identification of Novel Prognostic Markers and Their Clinical Application)
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Review

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15 pages, 2806 KiB  
Review
Leveraging Vector-Based Gene Disruptions to Enhance CAR T-Cell Effectiveness
by Beatriz C. Oliveira, Saaurav Bari and J. Joseph Melenhorst
Cancers 2025, 17(3), 383; https://doi.org/10.3390/cancers17030383 - 24 Jan 2025
Viewed by 1739
Abstract
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough in the treatment of relapsed and refractory B-cell malignancies, such as chronic lymphocytic leukemia (CLL), inducing long-term, sometimes curative, responses. However, fewer than 30% of CLL patients achieve such outcomes. It has been [...] Read more.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough in the treatment of relapsed and refractory B-cell malignancies, such as chronic lymphocytic leukemia (CLL), inducing long-term, sometimes curative, responses. However, fewer than 30% of CLL patients achieve such outcomes. It has been shown that a smaller subset of T cells capable of expansion and persistence is crucial for treatment effectiveness. Notably, a pre-existing mutation in the epigenetic regulator TET2, combined with CAR vector-induced disruption of the other intact allele, significantly enhanced the potency of the CAR-engineered T-cell clone in one CLL patient. This finding aligns with independent research, suggesting that the CAR gene’s genomic insertion site influences tumor-targeting capability. Thus, it is plausible that vector-induced gene disruptions affect CAR T-cell function. This review synthesizes existing knowledge on vector integration into the host genome and its impact on clinical outcomes in CAR T-cell therapy patients. Our aim is to inform the development of improved therapies and enhance their overall efficacy. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: Identification of Novel Prognostic Markers and Their Clinical Application)
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