V(D)J Recombination Excision Circles of B- and T-cells as Prognostic Marker in B-Cell Chronic Lymphocytic Leukemia

LYMPHOID TUMORS , , , ,

IV Obraztsov1,2, MA Gordukova 3, NA Severina4, BV Biderman4, SYu Smirnova4, AB Sudarikov4, EA Nikitin5, AG Rumyantsev1

1 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the Ministry of Health of the Russian Federation, 1 Samory Mashela str., Moscow, Russian Federation, 117198

2 AN Ryzhikh State Scientific Center for Coloproctology under the Ministry of Health of the Russian Federation, 2 Salyama Adilya str., Moscow, Russian Federation, 123423

3 GN Speranskii Municipal Children’s Hospital No. 9, 29 Shmitovskii pr-d, Moscow, Russian Federation, 123317

4 Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

5 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

For correspondence: Igor’ Vladimirovich Obraztsov, junior researcher, 1 Samory Mashela str., Moscow, Russian Federation, 117997; е-mail: igor_obraztsov@yahoo.com

For citation: Obraztsov IV, Gordukova MA, Severina NA, et al. V(D)J Recombination Excision Circles of B- and T-cells as Prognostic Marker in B-Cell Chronic Lymphocytic Leukemia. Clinical oncohematology. 2017;10(2):131–40 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-131-140

ABSTRACT

Background & Aims. T-cell receptor excision circles (TREC) and κ-deleting recombination excision circles (KREC) are extrachromosomal DNA segments generated during V(D)J re combination process that characterize the diversity of the antigen repertoire of T- and B-cells. The aim of our study is to identify the prognostic value of the excision circles in the chronic lymphocytic leukemia (CLL) setting.

Methods. The excision circles’ levels were assessed by means of real time PCR in 109 patients with high-risk CLL and 16 matched healthy individuals.

Results. KREC levels were signifi cantly (p < 0.001) lower in CLL patients vs. the reference group. TREC levels were lower in groups with unmutated status of immunoglobulin heavy chain variable region genes (p < 0.05) and 11q deletions (p < 0.1). Moreover, the KREC levels were higher in NOTCH1 mutation carriers than in noncarriers (p < 0.05). The comparison of treatment outcomes demonstrated a correlation between a high TREC level and achievement of complete remission. The prognostic value of the biomarker was confirmed by ROC-analysis: AUCTREC = 0.713 (p = 0.001)

Conclusion. Association between excision circles’ levels and clinical/laboratory CLL prognostic factors, as well as complete remission achievement, makes possible the implementation of the test for early prediction of the treatment outcome.

Key words: CLL, TREC, KREC, naive T-cells, naive B-cells, biomarkers, outcome predictors.

Received: November 10, 2016

Accepted: January 13, 2017

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