BIRC3 alterations in chronic and B‑cell acute lymphocytic leukemia patients

Alhourani,Eyad; Othman,Moneeb A.K.; Melo,Joana B.; Carreira,Isabel M.; Grygalewicz,Beata; Vujić,Dragana; Zecević,Zeljko; Joksić,Gordana; Glaser,Anita; Pohle,Beate; Schlie,Cordula; Hauke,Sven; Liehr,Thomas

doi:10.3892/ol.2016.4388

BIRC3 alterations in chronic and B‑cell acute lymphocytic leukemia patients

Authors:
- Eyad Alhourani
- Moneeb A.K. Othman
- Joana B. Melo
- Isabel M. Carreira
- Beata Grygalewicz
- Dragana Vujić
- Zeljko Zecević
- Gordana Joksić
- Anita Glaser
- Beate Pohle
- Cordula Schlie
- Sven Hauke
- Thomas Liehr
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Affiliations: Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena D-07743, Germany, Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra 3000‑548, Portugal, Cytogenetic Laboratory, Maria Sklodowska‑Curie Memorial Cancer Centre and Institute, Warsaw 02‑781, Poland, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia, Institute for Medical Care of Mother and Child of Serbia ‘Dr Vukan Cupic’, Belgrade 11070, Serbia, Vinca Institute of Nuclear Sciences, Belgrade 11001, Serbia, ZytoVision GmbH, Bremerhaven D-27572, Germany
Published online on: March 29, 2016 https://doi.org/10.3892/ol.2016.4388
Pages: 3240-3246
Copyright: © Alhourani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Deletions within chromosome 11q22‑23, are considered among the most common chromosomal aberrations in chronic lymphocytic leukemia (CLL), and are associated with a poor outcome. In addition to the ataxia telangiectasia mutated (ATM) gene, the baculoviral IAP repeat‑containing 3 (BIRC3) gene is also located in the region. BIRC3 encodes a negative regulator of the non‑canonical nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) protein. Disruption of BIRC3 is known to be restricted to CLL fludarabine‑refractory patients. The aim of the present study was to determine the frequency of copy number changes of BIRC3 and to assess its association with two known predictors of negative CLL outcome, ATM and tumor protein 53 (TP53) gene deletions. To evaluate the specificity of BIRC3 alterations to CLL, BIRC3 copy numbers were assessed in 117 CLL patients in addition to 45 B‑cell acute lymphocytic leukemia (B‑ALL) patients. A commercially available multiplex ligation dependent probe amplification kit, which includes four probes for the detection of TP53 and four probes for ATM gene region, was applied. Interphase‑directed fluorescence in situ hybridization was used to apply commercially available probes for BIRC3, ATM and TP53. High resolution array‑comparative genomic hybridization was conducted in selected cases. Genetic abnormalities of BIRC3 were detected in 23/117 (~20%) of CLL and 2/45 (~4%) of B‑ALL cases. Overall, 20 patients with CLL and 1 with B‑ALL possessed a BIRC3 deletion, whilst 3 patients with CLL and 1 with B‑ALL harbored a BIRC3 duplication. All patients with an ATM deletion also carried a BIRC3 deletion. Only 2 CLL cases possessed deletions in BIRC3, ATM and TP53 simultaneously. Evidently, the deletion or duplication of BIRC3 may be observed rarely in B‑ALL patients. BIRC3 duplication may occur in CLL patients, for which the prognosis requires additional studies in the future. The likelihood that TP53 deletions occur simultaneously with BIRC3 and/or ATM aberrations is low. However, as ATM deletions may, but not always, associate with BIRC3 deletions, each region should be considered in the future diagnostics of CLL in order to aid treatment decisions, notably whether to treat with or without fludarabine.

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1	Rodríguez-Vicente AE, Díaz MG and Hernández-Rivas JM: Chronic lymphocytic leukemia: A clinical and molecular heterogenous disease. Cancer Genet. 206:49–62. 2013. View Article : Google Scholar : PubMed/NCBI
2	Alhourani E, Rincic M, Othman MA, Pohle B, Schlie C, Glaser A and Liehr T: Comprehensive chronic lymphocytic leukemia diagnostics by combined multiplex ligation dependent probe amplification (MLPA) and interphase fluorescence in situ hybridization (iFISH). Mol Cytogenet. 7:792014. View Article : Google Scholar : PubMed/NCBI
3	Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, Döhner K, Bentz M and Lichter P: Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 343:1910–1916. 2000. View Article : Google Scholar : PubMed/NCBI
4	Gunn SR, Hibbard MK, Ismail SH, Lowery-Nordberg M, Mellink CH, Bahler DW, Abruzzo LV, Enriquez EL, Gorre ME, Mohammed MS and Robetorye RS: Atypical 11q deletions identified by array CGH may be missed by FISH panels for prognostic markers in chronic lymphocytic leukemia. Leukemia. 23:1011–1017. 2009. View Article : Google Scholar : PubMed/NCBI
5	Greipp PT, Smoley SA, Viswanatha DS, Frederick LS, Rabe KG, Sharma RG, Slager SL, Van Dyke DL, Shanafelt TD, Tschumper RC and Zent CS: Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis. Br J Haematol. 163:326–333. 2013. View Article : Google Scholar : PubMed/NCBI
6	Campregher PV and Hamerschlak N: Novel prognostic gene mutations identified in chronic lymphocytic leukemia and their impact on clinical practice. Clin Lymphoma Myeloma Leuk. 14:271–276. 2014. View Article : Google Scholar : PubMed/NCBI
7	Rossi D, Fangazio M, Rasi S, Vaisitti T, Monti S, Cresta S, Chiaretti S, Del Giudice I, Fabbri G, Bruscaggin A, et al: Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood. 119:2854–2862. 2012. View Article : Google Scholar : PubMed/NCBI
8	Rossi D, Fangazio M and Gaidano G: The spectrum of genetic defects in chronic lymphocytic leukemia. Mediterr J Hematol Infect Dis. 4:e20120762012. View Article : Google Scholar : PubMed/NCBI
9	Rossi D, Rasi S, Spina V, Bruscaggin A, Monti S, Ciardullo C, Deambrogi C, Khiabanian H, Serra R, Bertoni F, et al: Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood. 121:1403–1412. 2013. View Article : Google Scholar : PubMed/NCBI
10	Puiggros A, Blanco G and Espinet B: Genetic abnormalities in chronic lymphocytic leukemia: Where we are and where we go. BioMed Res Int. 2014:4359832014. View Article : Google Scholar : PubMed/NCBI
11	Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR and Kipps TJ: International Workshop on Chronic Lymphocytic Leukemia: Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 111:5446–5456. 2008. View Article : Google Scholar : PubMed/NCBI
12	Othman MA, Rincic M, Melo JB, Carreira IM, Alhourani E, Hunstig F, Glaser A and Liehr T: Novel cryptic three-way translocation t(2;9;18)(p23.2;p21.3;q21.33) with deletion of tumor suppressor genes in 9p21.3 and 13q14 in a T-cell acute lymphoblastic leukemia. Leukemia Res Treat. 2014:3571232014.
13	Rossi D, Ciardullo C, Spina V and Gaidano G: Molecular bases of chronic lymphocytic leukemia in light of new treatments. Immunol Lett. 155:51–55. 2013. View Article : Google Scholar : PubMed/NCBI
14	Cortese D, Sutton LA, Cahill N, Smedby KE, Geisler C, Gunnarsson R, Juliusson G, Mansouri L and Rosenquist R: On the way towards a ‘CLL prognostic index’: Focus on TP53, BIRC3, SF3B1, NOTCH1 and MYD88 in a population-based cohort. Leukemia. 28:710–713. 2014. View Article : Google Scholar : PubMed/NCBI
15	Morgan JA, Yin Y, Borowsky AD, Kuo F, Nourmand N, Koontz JI, Reynolds C, Soreng L, Griffin CA, Graeme-Cook F, et al: Breakpoints of the t(11;18)(q21;q21) in mucosa-associated lymphoid tissue (MALT) lymphoma lie within or near the previously undescribed gene MALT1 in chromosome 18. Cancer Res. 59:6205–6213. 1999.PubMed/NCBI
16	Shao L, Kang SH, Li J, Hixson P, Taylor J, Yatsenko SA, Shaw CA, Milosavljevic A, Chang CC, Cheung SW and Patel A: Array comparative genomic hybridization detects chromosomal abnormalities in hematological cancers that are not detected by conventional cytogenetics. J Mol Diagn. 12:670–679. 2010. View Article : Google Scholar : PubMed/NCBI
17	Specchia G, Albano F, Anelli L, Storlazzi CT, Monaco M, Capalbo S, Rocchi M and Liso V: Concomitant tetrasomy 3q and trisomy 18 in CD5(−), CD13(+) chronic lymphocytic leukemia. Cancer Genet Cytogenet. 133:160–163. 2002. View Article : Google Scholar : PubMed/NCBI
18	Kebriaei P, Anastasi J and Larson RA: Acute lymphoblastic leukaemia: Diagnosis and classification. Best Pract Res Clin Haematol. 15:597–621. 2002. View Article : Google Scholar : PubMed/NCBI
19	Ryan KM, Ernst MK, Rice NR and Vousden KH: Role of NF-kappaB in p53-mediated programmed cell death. Nature. 404:892–897. 2000. View Article : Google Scholar : PubMed/NCBI
20	Keller U, Huber J, Nilsson JA, Fallahi M, Hall MA, Peschel C and Cleveland JL: Myc suppression of Nfkb2 accelerates lymphomagenesis. BMC Cancer. 10:348–358. 2010. View Article : Google Scholar : PubMed/NCBI
21	Liu F, Bardhan K, Yang D, Thangaraju M, Ganapathy V, Waller JL, Liles GB, Lee JR and Liu K: NF-κB directly regulates Fas transcription to modulate Fas-mediated apoptosis and tumor suppression. J Biol Chem. 287:25530–25540. 2012. View Article : Google Scholar : PubMed/NCBI
22	Cox MC, Panetta P, Lo-Coco F, Del Poeta G, Venditti A, Maurillo L, Del Principe MI, Mauriello A, Anemona L, Bruno A, et al: Chromosomal aberration of the 11q23 locus in acute leukemia and frequency of MLL gene translocation: Results in 378 adult patients. Am J Clin Pathol. 122:298–306. 2004. View Article : Google Scholar : PubMed/NCBI
23	Monni O and Knuutila S: 11q deletions in hematological malignancies. Leuk Lymphoma. 40:259–266. 2001. View Article : Google Scholar : PubMed/NCBI
24	Strefford JC, Sutton LA, Baliakas P, Agathangelidis A, Malčíková J, Plevova K, Scarfó L, Davis Z, Stalika E, Cortese D, 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. 27:2196–2199. 2013. View Article : Google Scholar : PubMed/NCBI
25	Rose-Zerilli MJ, Forster J, Parker H, Parker A, Rodríguez AE, Chaplin T, Gardiner A, Steele AJ, Collins A, Young BD, et al: ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: Data from the UK LRF CLL4 trial. Haematologica. 99:736–742. 2014. View Article : Google Scholar : PubMed/NCBI
26	Goorha S, Glenn MJ, Drozd-Borysiuk E and Chen Z: A set of commercially available fluorescent in-situ hybridization probes efficiently detects cytogenetic abnormalities in patients with chronic lymphocytic leukemia. Genet Med. 6:48–53. 2004. View Article : Google Scholar : PubMed/NCBI