Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous type of non-Hodgkin lymphoma (NHL) that, in general, is associated with a poor clinical outcome. Therefore, a current major challenge is the discovery of new prognostic tools for this disease. In the present study, a cohort of 122 patients with PTCL was collected from a multicentric T-cell lymphoma consortium (TENOMIC). We analyzed the expression of 80 small nucleolar RNAs (snoRNAs) using high-throughput quantitative PCR. We demonstrate that snoRNA expression analysis may be useful in both the diagnosis of some subtypes of PTCL and the prognostication of both PTCL-not otherwise specified (PTCL-NOS; n ؍ 26) and angio-immunoblastic T-cell lymphoma (AITL; n ؍ 46) patients treated with chemotherapy. Like miRNAs, snoRNAs are globally down-regulated in tumor cells compared with their normal counterparts. In the present study, the snoRNA signature was robust enough to differentiate anaplastic large cell lymphoma (n ؍ 32) from other PTCLs. For PTCL-NOS and AITL, we obtained 2 distinct prognostic signatures with a reduced set of 3 genes. Of particular interest was the prognostic value of HBII-239 snoRNA, which was significantly overexpressed in cases of AITL and PTCL-NOS that had favorable outcomes. Our results suggest that snoRNA expression profiles may have a diagnostic and prognostic significance for PTCL, offering new tools for patient care and follow-up. (Blood. 2012;120(19):3997-4005)
. (2011) The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood, 117, 563-574. Hofbauer, S.W., Pinon, J.D., Brachtl, G., Haginger, L., Wang, W., Johrer, K., Tinhofer, I., Hartmann, T.N. & Greil, R. (2010) Small nucleolar RNA expression profiles refine the prognostic impact of IGHV mutational status on treatment-free survival in chronic lymphocytic leukaemiaChronic B-cell lymphocytic leukaemia (CLL) is generally an indolent disease, with most patients surviving years without treatment although some progress more rapidly. Several markers, such as IGHV mutational status (Hamblin et al, 1999), cytogenetic abnormalities (D€ ohner et al, 2000) and recurrent gene mutations (Wang et al, 2011;Jeromin et al, 2014), have helped to better stratify patient risk, but few are routinely used by clinicians and they are still relatively unreliable, reflecting the clinical and physiopathological heterogeneity of the disease. Thus there remains room for improvement and new molecular markers. Our understanding of the various roles of small nucleolar RNAs (snoRNAs) in cancer is continually expanding. Besides their well-known function in ribosomal RNA modifications, snoRNAs have recently been described as new biomarkers in haematological cancers (Ronchetti et al, 2012(Ronchetti et al, , 2013 Valleron et al, 2012a,b). Notably, Ronchetti et al (2013) studied a cohort of Binet stage A CLL patients, reporting that a specific snoRNA signature was predictive of outcome for early stage CLL. In this study, we investigated the snoRNA expression profiles in CLL patients fully annotated for both the classical prognostic markers (IGHV mutational status, cytogenetic abnormalities, Binet stage) and recurrent somatic mutations (TP53, NOTCH1, SF3B1). The methods and patient characteristics are described in Data S1, Tables SI and SII. Using high-throughput quantitative polymerase chain reaction (Fluidigm, Les Ullis, France), we first determined whether snoRNA profiling (n = 221, covering more than two-thirds of previously described snoRNAs) could discriminate between CLL prognostic subgroups in an exploration set of 58 treatment-naive CLL and five normal B-cells. Unsupervised hierarchical clustering showed that patients did not cluster together when considering criteria such as IGHV mutational status, Binet stage, age, gender, karyotype, fluorescence in situ hybridization and NOTCH1/ TP53/SF3B1mutation, but instead were scattered along the dendrogram (Fig S1). Supervised analysis also did not find a snoRNA signature specific to the conventional clinico-biological parameters, suggesting that snoRNA expression profiles were not associated with the aforementioned factors impacting on CLL outcome. The apparent contradiction between our results and those reported by Ronchetti et al (2013) could be explained by the differences between the two cohorts as we included more cases presenting adverse prognosis factors.However, the unsupervised analysis showed that...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.