Submicroscopic Deletions of Immunoglobulin Heavy Chain Gene (IGH) in Precursor B Lymphoblastic Leukemia with IGH Rearrangements
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5´ variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3´ IGH signal were detected. Thus, submicroscopic deletion of the IGH 5´ variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5´ variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.
Abstract
Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5´ variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3´ IGH signal were detected. Thus, submicroscopic deletion of the IGH 5´ variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5´ variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.
참고문헌 (17)
- Swerdlow SH, "WHO classification of tumours of haematopoietic and lymphoid tissues" (2008), IARC
- Meloni-Ehrig A., "The principles of clinical cytogenetics", pp.309~370 (2013), Springer
- Dyer MJ, "Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers?", Blood, 115, pp.1490~1499 (2010)
- Akasaka T, "Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)", Blood, 109, pp.3451~3461 (2007)
- Harrison CJ, "Cytogenetics of paediatric and adolescent acute lymphoblastic leukaemia", Br J Haematol, 144, pp.147~156 (2009)
- Chapiro E, "Chromosomal translocations involving the IGH@ locus in B-cell precursor acute lymphoblastic leukemia: 29 new cases and a review of the literature", Cancer Genet, 206, pp.162~173 (2013)
- Moorman AV, "IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia", J Clin Oncol, 30, pp.3100~3108 (2012)
- Wlodarska I, "Telomeric IGH losses detectable by fluorescence in situ hybridization in chronic lymphocytic leukemia reflect somatic VH recombination events", J Mol Diagn, 9, pp.47~54 (2007)
- Trakhtenbrot L, "Correlation between losses of IGH or its segments and deletions of 13q14 in t(11;14) (q13;q32) multiple myeloma", Genes Chromosomes Cancer, 49, pp.17~27 (2010)
- Fink SR, "Fluorescent-labeled DNA probes applied to novel biological aspects of B-cell chronic lymphocytic leukemia", Leuk Res, 29, pp.253~262 (2005)
- Hwang Y, "Various patterns of IgH deletion identified by FISH using combined IgH and IgH", CCND1 probes in multiple myeloma and chronic lymphocytic leukemia, 2011, pp.33, 299~304
- Quintero-Rivera F, "Frequency of 5´ IGH deletions in B-cell chronic lymphocytic leukemia", Cancer Genet Cytogenet, 190, pp.33~39 (2009)
- Hutspardol S, "Interphase-FISH screening for eight common rearrangements in pediatric B-cell precursor acute lymphoblastic leukemia", Int J Lab Hematol, 35, pp.406~415 (2013)
- Dyer MJ, "Unusual deletions within the immunoglobulin heavy-chain locus in acute leukemias", Blood, 82, pp.865~871 (1993)
- Paulsson K, "Identification of cryptic aberrations and characterization of translocation breakpoints using array CGH in high hyperdiploid childhood acute lymphoblastic leukemia", Leukemia, 20, pp.2002~2007 (2006)
- Shaffer LG, "An international System for human cytogenetic nomenclature" (2013), S. Karger
- Reindl L, "Biological and clinical characterization of recurrent 14q deletions in CLL and other mature B-cell neoplasms", Br J Haematol, 151, pp.25~36 (2010)
