TY - JOUR
T1 - Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy
T2 - results from the HOVON 109 study
AU - Saberi Hosnijeh, Fatemeh
AU - van der Straten, Lina
AU - Kater, Arnon P.
AU - van Oers, Marinus H.J.
AU - Posthuma, Ward F.M.
AU - Chamuleau, Martine E.D.
AU - Bellido, Mar
AU - Doorduijn, Jeanette K.
AU - van Gelder, Michel
AU - Hoogendoorn, Mels
AU - de Boer, Fransien
AU - te Raa, G. Doreen
AU - Kerst, J. Martijn
AU - Marijt, Erik W.A.
AU - Raymakers, Reinier A.P.
AU - Koene, Harry R.
AU - Schaafsma, Martijn R.
AU - Dobber, Johan A.
AU - Tonino, Sanne H.
AU - Kersting, Sabina S.
AU - Langerak, Anton W.
AU - Levin, Mark David
N1 - 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
PY - 2020/9
Y1 - 2020/9
N2 - 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 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.
AB - 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 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.
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Agents/therapeutic use
KW - Biomarkers, Tumor/blood
KW - Chlorambucil
KW - Disease-Free Survival
KW - Female
KW - Gene Expression
KW - Humans
KW - Immunoglobulin Heavy Chains/blood
KW - Immunotherapy/methods
KW - Lenalidomide
KW - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis
KW - Male
KW - Middle Aged
KW - Mutation
KW - Prognosis
KW - Proteinase Inhibitory Proteins, Secretory/blood
KW - Proteomics/methods
KW - Receptors, IgE/blood
KW - Rituximab
KW - Signaling Lymphocytic Activation Molecule Family/blood
KW - Treatment Outcome
KW - Tumor Necrosis Factor Receptor Superfamily, Member 7/blood
UR - http://www.scopus.com/inward/record.url?scp=85089975568&partnerID=8YFLogxK
U2 - 10.1016/j.exphem.2020.08.002
DO - 10.1016/j.exphem.2020.08.002
M3 - Article
C2 - 32781097
AN - SCOPUS:85089975568
SN - 0301-472X
VL - 89
SP - 55-60.e6
JO - Experimental Hematology
JF - Experimental Hematology
ER -