Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B‐cell receptor signalling

Friedman, Daphne R.; Guadalupe, Eross; Volkheimer, Alicia D.; Moore, Joseph O.; Weinberg, J. Brice

doi:10.1111/bjh.15632

Cited by 9 publications

(8 citation statements)

References 22 publications

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“…Therefore, CD5 is currently considered one of the characteristic antigens of malignant T cells [8]. In addition, CD5 is also expressed in some B cell malignancies [27, 28]. Clinical trials using anti-CD5 monoclonal antibody have revealed a moderate therapeutic effect in patients with cutaneous T cell lymphomas (CTCLs) or chronic lymphocyte leukemia (CLL) [29, 30].…”

Section: Introductionmentioning

confidence: 99%

2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies

et al. 2019

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Background: Chimeric antigen receptor engineered T cells (CAR-T) have demonstrated extraordinary efficacy in B cell malignancy therapy and have been approved by the US Food and Drug Administration for diffuse large B cell lymphoma and acute B lymphocytic leukemia treatment. However, treatment of T cell malignancies using CART cells remains limited due to the shared antigens between malignant T cells and normal T cells. CD5 is considered one of the important characteristic markers of malignant T cells and is expressed on almost all normal T cells but not on NK-92 cells. Recently, NK-92 cells have been utilized as CAR-modified immune cells. However, in preclinical models, CART cells seem to be superior to CAR-NK-92 cells. Therefore, we speculate that in addition to the short lifespan of NK-92 cells in mice, the costimulatory domain used in CAR constructs might not be suitable for CAR-NK-92 cell engineering. Methods: Two second-generation anti-CD5 CAR plasmids with different costimulatory domains were constructed, one using the T-cell-associated activating receptor-4-1BB (BB.z) and the other using a NK-cell-associated activating receptor-2B4 (2B4.z). Subsequently, BB.z-NK and 2B4.z-NK were generated. Specific cytotoxicity against CD5 + malignant cell lines, primary CD5 + malignant cells, and normal T cells was evaluated in vitro. Moreover, a CD5 + T cell acute lymphoblastic leukemia (T-ALL) mouse model was established and used to assess the efficacy of CD5-CAR NK immunotherapy in vivo. Results: Both BB.z-NK and 2B4.z-NK exhibited specific cytotoxicity against CD5 + malignant cells in vitro and prolonged the survival of TALL xenograft mice. Encouragingly, 2B4.z-NK cells displayed greater anti-CD5 + malignancy capacity than that of BB.z-NK, accompanied by a greater direct lytic side effect versus BB.z-NK. Conclusions: Anti-CD5 CAR-NK cells, particularly those constructed with the intracellular domain of NK-cellassociated activating receptor 2B4, may be a promising strategy for T cell malignancy treatment.

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Section: Introductionmentioning

confidence: 99%

2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies

et al. 2019

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“…The diagnostic criteria for CD5-negative CLL is an important issue. Several studies have established a diagnosis of CD5-negative CLL where fewer than 5% of leukemic cells demonstrated CD5 expression [ 41 , 42 , 43 , 44 , 45 ]. CD5-negative B-CLL seems to have a different clinical presentation to CD5-positive CLL ( Table 1 ) [ 41 , 42 , 43 , 44 , 45 , 46 ].…”

Section: Atypical Immunophenotypementioning

confidence: 99%

Atypical Chronic Lymphocytic Leukemia—The Current Status

Robak,

Krawczyńska,

Cebula-Obrzut

et al. 2023

Cancers

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A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL, the coexistence of CD19, CD20, CD5, and CD23, the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophenotypically. Morphologically atypical CLL cells have been defined mainly as large, atypical forms, prolymphocytes, or cleaved cells. However, current aCLL diagnostics rely more on immunophenotypic characteristics rather than atypical morphology. Immunophenotypically, atypical CLL differs from classic CLL in the lack of expression of one or fewer surface antigens, most commonly CD5 and CD23, and the patient does not meet the criteria for a diagnosis of any other B-cell lymphoid malignancy. Morphologically atypical CLL has more aggressive clinical behavior and worse prognosis than classic CLL. Patients with aCLL are more likely to display markers associated with poor prognosis, including trisomy 12, unmutated IGVH, and CD38 expression, compared with classic CLL. However, no standard or commonly accepted criteria exist for differentiating aCLL from classic CLL and the clinical significance of aCLL is still under debate. This review summarizes the current state of knowledge on the morphological, immunophenotypic, and genetic abnormalities of aCLL.

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“…However, Friedman et al [18] analyzed the correlation between mean fluorescence intensity of the CD5 antigen in a population of leukemic cells and a clinical course of the disease in a group of 423 patients suffering from CLL. It was shown that high MFI rate correlates with longer progression-free survival.…”

Section: Cd5-negative Cllmentioning

confidence: 99%

Atypical immunophenotype of chronic lymphocytic leukemia

et al. 2022

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Assessment of the immunophenotype plays a crucial role in the diagnostic process of chronic lymphocytic leukemia (CLL). The expression of CD5, CD19 and CD23 antigens with a concomitant reduction or lack of surface immunoglobulin expression as well as CD22 and CD79b antigens is the basic part of CLL diagnosis. A significant diagnostic challenge is atypical CLL with cells devoid of CD5 or CD23 antigens. The assessment of additional antigens in flow cytometry, especially the CD200 glycoprotein, may facilitate the process of differential diagnosis of atypical CLL from other B-cell lymphoproliferative neoplasms. The results of current studies analyzing the influence of atypical CLL on prognosis are inconclusive. The analysis of a large group of patients with atypical CLL is difficult because of the rare occurrence of CD5(-) or CD23(-) CLL and the misdiagnosis of this disease as other B-cell lymphoproliferative neoplasms.The following paper aims to show how important it is to include atypical CLL in the diagnostic process of this disease and to re-standardize the commonly used immunophenotypic scales for its diagnosis.

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Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B‐cell receptor signalling

Cited by 9 publications

References 22 publications

2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies

2B4 costimulatory domain enhancing cytotoxic ability of anti-CD5 chimeric antigen receptor engineered natural killer cells against T cell malignancies

Atypical Chronic Lymphocytic Leukemia—The Current Status

Atypical immunophenotype of chronic lymphocytic leukemia

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