Dataset Information

The Proteome Landscape of Chronic Lymphocytic Leukemia

ABSTRACT: Many functional consequences of mutations on tumor phenotypes in chronic lymphocytic leukemia (CLL) are only partially known. This is in part due to missing information on the proteome of CLL. We profiled the proteome of 49 diverse CLL samples with data-independent acquisition mass spectrometry (DIA-MS) and related the results to genomic, functional and clinical differences. We found trisomy 12 and IGHV to be major determinants of proteome variation in CLL (1073 and 512 differential proteins). In contrast to reports in other biological systems, the disease driver trisomy 12 was associated with limited protein buffering, a finding that suggests the biological relevance of proteins encoded by chromosome 12 for CLL biology. Protein complex analyses detected functional units involved in BCR/PI3K/AKT signaling in CLL with trisomy 12. We identified the transcription factor complex of STAT1/STAT2 to be up-regulated in IGHV unmutated CLL. We tested the functional relevance of protein expression for associations with response to anticancer drugs, and STAT2 protein expression emerged as a biomarker for the prediction of response to kinase inhibitors including BTK and MEK inhibitors. This study highlights the emerging importance of protein abundance profiling in cancer research and identifies STAT2 protein levels as new key factor in CLL biology.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Blood

DISEASE(S): Chronic Lymphocytic Leukemia

SUBMITTER: Ben Collins

LAB HEAD: Ben Collins

PROVIDER: PXD022216 | Pride | 2021-09-27

REPOSITORIES: Pride

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Publications

The protein landscape of chronic lymphocytic leukemia.

Meier-Abt Fabienne F Lu Junyan J Cannizzaro Ester E Pohly Marcel F MF Kummer Sandra S Pfammatter Sibylle S Kunz Laura L Collins Ben C BC Nadeu Ferran F Lee Kwang Seok KS Xue Peng P Gwerder Myriam M Roiss Michael M Hüllein Jennifer J Scheinost Sebastian S Dietrich Sascha S Campo Elias E Huber Wolfgang W Aebersold Ruedi R Zenz Thorsten T

Blood 20211201 24

Many functional consequences of mutations on tumor phenotypes in chronic lymphocytic leukemia (CLL) are unknown. This may be in part due to a scarcity of information on the proteome of CLL. We profiled the proteome of 117 CLL patient samples with data-independent acquisition mass spectrometry and integrated the results with genomic, transcriptomic, ex vivo drug response, and clinical outcome data. We found trisomy 12, IGHV mutational status, mutated SF3B1, trisomy 19, del(17)(p13), del(11)(q22.3 ...[more]

PMID: 34189564

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Project description:Prospective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. Trisomy 12, 11q- and 17p- abnormalities were scanty and of no predictive value in both conditions. Notably, gene and miRNA expression profiling showed no significant differences between cMBL and Rai0-CLL. Furthermore, similar gene and miRNA expression signatures were found in cMBL and Rai0-CLL according to the IGHV gene mutational status: that is, unmutated cases had different signatures from mutated cases, irrespectively of the cMBL or CLL condition. Overall, our study based on a prospective series of patients indicates that no major biological differences exist in cMBL compared to Rai0-CLL, suggesting that this two entities mainly differ for the initial size of the monoclonal cell population which may reflect in the longer time for clonal expansion. This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 160 patients (Binet stage A) including 45 cMBL and 115 Rai0-CLL. Peripheral blood mononuclear cells from CLL patients were isolated by Ficoll-Hypaque (Seromed, Biochrom KG, Berlin, Germany) density-gradient centrifugation. For gene and miRNA expression profiling experiments CLL cells were enriched by negative selection with the EasySep-Human B cell enrichment kit without CD43 depletion (Stem Cell Technologies) using the fully automated protocol of immunomagnetic cell separation with RoboSepTM (Stem Cell Technologies).

Dataset Information

The Proteome Landscape of Chronic Lymphocytic Leukemia

Publications

The protein landscape of chronic lymphocytic leukemia.

Similar Datasets

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