Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study
Saberi Hosnijeh, Fatemeh; van der Straten, Lina; Kater, Arnon P.; van Oers, Marinus H.J.; Posthuma, Ward F.M.; Chamuleau, Martine E.D.; Bellido, Mar; Doorduijn, Jeanette K.; van Gelder, Michel; Hoogendoorn, Mels; de Boer, Fransien; te Raa, G. Doreen; Kerst, J. Martijn; Marijt, Erik W.A.; Raymakers, Reinier A.P.; Koene, Harry R.; Schaafsma, Martijn R.; Dobber, Johan A.; Tonino, Sanne H.; Kersting, Sabina S.; Langerak, Anton W.; Levin, Mark David
(2020) Experimental Hematology, volume 89, pp. 55 - 60.e6
(Article)
Abstract
Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might
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be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25–60.9). Patients with high levels of sCD23 (>11.27, p = 0.026), sCD27 (>11.03, p = 0.04), SPINT1 (>1.6, p = 0.001), and LY9 (>8.22, p = 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients.
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Keywords: Aged, Aged, 80 and over, Antineoplastic Agents/therapeutic use, Biomarkers, Tumor/blood, Chlorambucil, Disease-Free Survival, Female, Gene Expression, Humans, Immunoglobulin Heavy Chains/blood, Immunotherapy/methods, Lenalidomide, Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis, Male, Middle Aged, Mutation, Prognosis, Proteinase Inhibitory Proteins, Secretory/blood, Proteomics/methods, Receptors, IgE/blood, Rituximab, Signaling Lymphocytic Activation Molecule Family/blood, Treatment Outcome, Tumor Necrosis Factor Receptor Superfamily, Member 7/blood, Genetics, Molecular Biology, Hematology, Cancer Research, Cell Biology, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article
ISSN: 0301-472X
Publisher: Elsevier Inc.
Note: Funding Information: This work was supported by an EU TRANSCAN/ Dutch Cancer Society grant (179; NOVEL consortium; to AWL) and an unrestricted research grant from Gilead Sciences, Netherlands BV (to AWL and FSH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. The authors acknowledge Martijn Kolijn, Erasmus MC, for critical discussions; Julie M. N. Dubois and Ingrid Derks, Academic Medical Center, Amsterdam, for sample preparation; Tamara Pesic, Erasmus MC, for IGHV sequencing; and Kirsten K. J. Gussinklo, Erasmus MC, for FISH analysis. None of the authors declared a conflict of interest. Funding Information: This work was supported by an EU TRANSCAN/ Dutch Cancer Society grant ( 179 ; NOVEL consortium; to AWL) and an unrestricted research grant from Gilead Sciences, Netherlands BV (to AWL and FSH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Publisher Copyright: © 2020 ISEH – Society for Hematology and Stem Cells
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