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Evaluation of Caspase-9b and PP2Ac?2 as potential biomarkers for chronic lymphocytic leukemia.

ABSTRACT: BACKGROUND:Disruption of alternative splicing in apoptotic factors has been associated to chronic lymphocytic leukemia among other cancers and hematological malignancies. The proapoptotic proteins Caspase-9 and PP2Ac? are functionally related in a direct interaction, which constitutes a promising target for cancer therapy. Both proteins present aberrant mRNA splicing variants that are antiapoptotic (Caspase-9b) and catalytically inactive (PP2Ac?2), respectively. RESULTS:In this work we have analyzed the relative abundance of the aberrant spliced forms Caspase-9b and PP2Ac?2 in several cell lines and chronic lymphocytic leukemia patients and correlated it with several parameters of the disease. Despite 40 % of the patients presented Caspase-9b dysregulation, there was no direct association between alterations in Caspase-9b relative abundance and the parameters analyzed in medical records. More importantly, PP2Ac?2 dysregulation was observed in 88 % of CLL patients and was related with advanced stages of the malignancy. CONCLUSIONS:Caspase-9b dysregulation seemed to be associated with the disease, although the differences between healthy donors and CLL patients were not statistically significant. However, PP2Ac?2 dysregulation was significantly different between healthy donors and CLL patients and correlated with Binet B and C stages; therefore, we propose the use of PP2Ac?2 dysregulation as a potential biomarker for advanced stages of chronic lymphocytic leukemia.

SUBMITTER: Dominguez-Berrocal L

PROVIDER: S-EPMC4857392 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Evaluation of Caspase-9b and PP2Acα2 as potential biomarkers for chronic lymphocytic leukemia.

Domínguez-Berrocal Leticia L Zhang Xiguang X Zini Jean Marc JM Fominaya Jesús J Rebollo Angelita A Bravo Jerónimo J

Biomarker research 20160504

<h4>Background</h4>Disruption of alternative splicing in apoptotic factors has been associated to chronic lymphocytic leukemia among other cancers and hematological malignancies. The proapoptotic proteins Caspase-9 and PP2Acα are functionally related in a direct interaction, which constitutes a promising target for cancer therapy. Both proteins present aberrant mRNA splicing variants that are antiapoptotic (Caspase-9b) and catalytically inactive (PP2Acα2), respectively.<h4>Results</h4>In this wo ...[more]

PMID: 27152197

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Project description:Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in highly purified cells from 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets. CLLs display a sno/scaRNAs expression profile similar to normal memory, naÃ¯ve and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups. These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients. This series of microarray experiments contains the gene expression profiles of purified B-cell chronic lymphocytic leukemia (B-CLL) cells obtained from 211 patients (Binet stage A), 6 normal controls from peripheral blood mononuclear cells (BC), and B-cell sub-populations from tonsils (3 naÃ¯ve B-cells (N), 2 marginal zone (MZ)-like, 3 switched memory (SM) B-cells and 4 germinal center (GC) ). 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

Evaluation of Caspase-9b and PP2Ac?2 as potential biomarkers for chronic lymphocytic leukemia.

Publications

Evaluation of Caspase-9b and PP2Acα2 as potential biomarkers for chronic lymphocytic leukemia.

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