BIRC3 alterations in chronic and B-cell acute lymphocytic leukemia patients.
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.BIRC3encodes a negative regulator of the non-canonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein. Disruption ofBIRC3is known to be restricted to CLL fludarabine-refractory patients. The aim of the present study was to determine the frequency of copy number changes ofBIRC3and to assess its association with two known predictors of negative CLL outcome,ATMand tumor protein 53 (TP53) gene deletions. To evaluate the specificity ofBIRC3alterations to CLL,BIRC3copy 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 ofTP53and four probes forATMgene region, was applied. Interphase-directed fluorescencein situhybridization was used to apply commercially available probes forBIRC3,ATMandTP53. High resolution array-comparative genomic hybridization was conducted in selected cases. Genetic abnormalities ofBIRC3were 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 aBIRC3deletion, whilst 3 patients with CLL and 1 with B-ALL harbored aBIRC3duplication. All patients with anATMdeletion also carried aBIRC3deletion. Only 2 CLL cases possessed deletions inBIRC3,ATMandTP53simultaneously. Evidently, the deletion or duplication ofBIRC3may be observed rarely in B-ALL patients.BIRC3duplication may occur in CLL patients, for which the prognosis requires additional studies in the future. The likelihood thatTP53deletions occur simultaneously withBIRC3and/orATMaberrations is low. However, asATMdeletions may, but not always, associate withBIRC3deletions, 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.
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena D-07743, Germany.
Eyad
E
Alhourani
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena D-07743, Germany.
Moneeb A K
MA
Othman
Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal; Research Centre for Environment, Genetics and Oncobiology, Coimbra 3000-548, Portugal.
Joana B
JB
Melo
Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal; Research Centre for Environment, Genetics and Oncobiology, Coimbra 3000-548, Portugal.
Isabel M
IM
Carreira
Cytogenetic Laboratory, Maria Sklodowska-Curie Memorial Cancer Centre and Institute, Warsaw 02-781, Poland.
Beata
B
Grygalewicz
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.
Dragana
D
Vujić
Institute for Medical Care of Mother and Child of Serbia 'Dr Vukan Cupic', Belgrade 11070, Serbia.
Zeljko
Z
Zecević
Vinca Institute of Nuclear Sciences, Belgrade 11001, Serbia.
Gordana
G
Joksić
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena D-07743, Germany.
Anita
A
Glaser
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena D-07743, Germany.
Beate
B
Pohle
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena D-07743, Germany.
Cordula
C
Schlie
ZytoVision GmbH, Bremerhaven D-27572, Germany.
Sven
S
Hauke
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena D-07743, Germany.
Thomas
T
Liehr
B-cell acute lymphocytic leukemia; baculoviral IAP repeat-containing 3 gene; chronic lymphocytic leukemia; copy number alterations; deletion; duplication; hyperdiploidy