Encyclopedia of CLL Subsets – a Unique Bioinformatics Tool and Database for Analysis of Subsets of Stereotypical B-Cell Receptors in CLL

Česká verze

Authors: T. Reigl ¹; K. Stránská ^1,2; V. Bystrý ¹; A. Krejčí ¹; A. Grioni ¹; Š. Pospíšilová ^1,2; N. Darzentas ¹; K. Plevová ^1,2
Authors place of work: CEITEC – Středoevropský technologický institut, Masarykova univerzita, Brno 2 Interní hematologická a onkologická klinika LF MU a FN Brno ¹
Published in the journal: Klin Onkol 2019; 32(Supplementum1): 167-170
Category: Článek ve sborníku

Summary

Background: Chronic lymphocytic leukemia (CLL) is clinically and biologically highly variable disease which is closely related with multiple cellular and molecular markers, including sequence motifs of B-cell receptors. These motifs are highly similar (stereotyped) within one third of CLL patients and create homogeneous groups called stereotyped CLL subsets. The homogeneity is reflected also in clinical and biological characteristics of the disease. To facilitate access to the information about individual subsets, we have created a publicly available web-based tool Encyclopedia of CLL Subsets.

Materials and methods: The Encyclopedia of CLL subsets belongs to our bioinformatics platform Antigen Receptor Research Tool (ARResT) developed for analysis, clustering, and annotation of immunoglobulin sequences. To gather primary knowledge about the subsets, we have analyzed a dataset of 7,500 CLL patients published by Agathangelidis et al in 2012 [1]. We have created an overview of major stereotyped subsets and their characteristics. Additional clinical and cytogenomic information about individual subsets has been obtained by machine text processing of available literature from server PubMed and is regularly updated.

Results: We have created a unique web-based application Encyclopedia of CLL Subsets available from http: //arrest.tools/subsets for an interactive access to the information about stereotyped CLL subsets. A user can obtain and compare basic information about the major subsets including their clinical and cytogenomic characteristics. These have been manually curated from machine processed results from PubMed database by experts in CLL research. Through the Encyclopedia’s user interface, user can also directly use our published tool ARResT/AssignSubsets to assign new immunoglobulin sequences to the major subsets.

Conclusion: The Encyclopedia of CLL Subsets is a publicly available online tool facilitating access to the most recent research knowledge about stereotyped CLL subsets and enabling analysis of own data and interpretation of the results. This gives the Encyclopedia a great potential for its use in clinical routine.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 1. 3. 2019

Accepted: 4. 3. 2019

Keywords:

Bioinformatics – immunogenetics – immunoglobulins – stereotyped BCR

Zdroje

1. Agathangelidis A, Darzentas N, Hadzidimitriou A et al. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood 2012; 119 (19): 4467–4475. doi: 10.1182/blood-2011-11-393694.

2. Bystry V, Agathangelidis A, Bikos V et al. ARResT/AssignSubsets: a novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy. Bioinformatics 2015; 31 (23): 3844–3846. doi: 10.1093/bioinformatics/btv456.

3. Baliakas P, Hadzidimitriou A, Sutton LA et al. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study. Lancet Haematol 2014; 1 (2): e74–e84. doi: 10.1016/S2352-3026 (14) 00005-2.

4. Visco C, Maura F, Tuana G et al. Immune thrombocytopenia in patients with chronic lymphocytic leukemia is associated with stereotyped B-cell receptors. Clin Cancer Res 2012; 18 (7): 1870–1878. doi: 10.1158/1078-0432.CCR-11-3019.

5. Maura F, Visco C, Falisi E et al. B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia. Am J Hematol 2013; 88 (1): 32–36. doi: 10.1002/ajh.23342.

6. Xochelli A, Baliakas P, Kavakiotis I et al. Chronic lymphocytic leukemia with mutated IGHV4-34 receptors: shared and distinct immunogenetic features and clinical outcomes. Clin Cancer Res 2017; 23 (17): 5292–5301. doi: 10.1158/1078-0432.CCR-16-3100.

7. Rossi D, Spina V, Cerri M et al. Stereotyped B-cell receptor is an independent risk factor of chronic lymphocytic leukemia transformation to Richter syndrome. Clin Cancer Res 2009; 15 (13): 4415–4422. doi: 10.1158/1078-0432.CCR-08-3266.

8. Sutton LA, Young E, Baliakas, P et al. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. Haematologica 2016; 101 (8): 959–967. doi: 10.3324/haematol.2016.141812.

9. Mansouri L, Sutton LA, Ljungström V et al. Functional loss of IB leads to NF-B deregulation in aggressive chronic lymphocytic leukemia. J Exp Med 2015; 212 (6): 833–843. doi: 10.1084/jem.20142009.

10. Strefford JC, Sutton LA, Baliakas P et al. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset# 2. Leukemia 2013; 27 (11): 2196–2199. doi: 10.1038/leu.2013.98.

11. Jeromin S, Haferlach C, Dicker F et al. Differences in prognosis of stereotyped IGHV3-21 chronic lymphocytic leukaemia according to additional molecular and cytogenetic aberrations. Leukemia 2016; 30 (11): 2251–2253. doi: 10.1038/leu.2016.189.

12. Navrkalova V, Young E, Baliakas P et al. ATM mutations in major stereotyped subsets of chronic lymphocytic leukemia: enrichment in subset# 2 is associated with markedly short telomeres. Haematologica 2016; 101 (9): e369–e373. doi: 10.3324/haematol.2016.142968.

13. Malcikova J, Stalika E, Davis Z et al. The frequency of TP 53 gene defects differs between chronic lymphocytic leukaemia subgroups harbouring distinct antigen receptors. Br J Haematol 2014; 166 (4): 621–625. doi: 10.1111/bjh.12893.