Five CCAAT-enhancer-binding-protein gene family members are deregulated by the immunoglobulin heavy chain locus in B-cell precursor acute lymphoblastic leukaemia
Russell, L.J., Akasaka, T., Balasas, T., Chaprio, E., Bernard, O., Siebert, R., Dyer, M.J. and Harrison, C.J. (2007) Five CCAAT-enhancer-binding-protein gene family members are deregulated by the immunoglobulin heavy chain locus in B-cell precursor acute lymphoblastic leukaemia. British Journal of Haematology, 137, (Supplement 1), 2-3. (doi:10.1111/j.1365-2141.2007.06557.x).
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Description/Abstract
Chromosomal translocations lead to oncogene activation in a
significant number of haematological malignancies. Those involving
the immunoglobulin heavy chain locus, IGH, at chromosome band
14q32 are frequently observed in B-cell malignant proliferation. A
small number have been described in B-cell precursor acute
lymphoblastic leukaemia (BCP-ALL). However, their biological and
clinical significance is currently unknown. Detailed fluorescence in
situ hybridisation (FISH) and molecular studies were carried out on
a series of BCP-ALL patients with chromosomal abnormalities
involving 14q32. Novel and recurrent translocations affecting different chromosomes were highlighted. Refined FISH mapping
identified putative IGH partner genes at, or flanking, the translocation
breakpoints. Four translocations: two previously reported,
t(14;19)(q32;q13), t(8;14)(q11;q32), and two novel, t(14;14)(q11;q32)/
inv(14)(q11q32) and t(14;20)(q32;q13), were identified. Molecular
analyses showed that four different members of the CAATT enhancer
binding protein (CEBP) gene family were involved: CEBPA (19q13,
n59), CEBPD (8q11, n58), CEBPE (14q11, n53) and CEBPB (20q13,
n52). One patient with a t(14;19)(q32;q13) was observed to involve
the fifth family member CEBPG (19q13, n51). Breakpoints were
located within the 30 untranslated region (UTR) of CEBPA and either
30 UTR or 50 of CEBPE, whereas breakpoints in 8q11 were B30 kb
centromeric of CEBPD. Where material was available, over-expression
of target genes was shown by quantitative real-time PCR.
Overall, this study has demonstrated for the first time the
involvement of five members of the same gene family in a single
subtype of haematological disease. It has indicated that transcriptional
upregulation of CEBP gene family members, by juxtaposition
to IGH, is important in BCP-ALL: a mechanism in complete contrast
to that involving CEPBA in acute myeloid leukaemia.
| Item Type: | Article |
|---|---|
| Additional Information: | Free Communications: Lymphoproliferative Disorders (p 1-88) |
| ISSNs: | 0007-1048 (print) |
| Related URLs: | |
| Keywords: | gene, time, locus, families, b cell |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Cancer Sciences |
| Item ID: | 62906 |
| Date Deposited: | 07 Oct 2008 |
| Last Modified: | 01 Jun 2011 00:39 |
| Contributors: | Russell, L.J. (Author) Akasaka, T. (Author) Balasas, T. (Author) Chaprio, E. (Author) Bernard, O. (Author) Siebert, R. (Author) Dyer, M.J. (Author) Harrison, C.J. (Author) |
| Date: | 2007 |
| Additional Information: | Free Communications: Lymphoproliferative Disorders (p 1-88) |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/62906 |
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