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The t(X;7)(q22;q34) in paediatric T-cell acute lymphoblastic leukaemia results in overexpression of the insulin receptor substrate 4 gene through illegitimate recombination with the T-cell receptor beta locus.

Karrman, Kristina LU ; Kjeldsen, Eigil; Lassen, Carin LU ; Isaksson, Margareth LU ; Davidsson, Josef LU ; Andersson, Anna LU ; Hasle, Henrik; Fioretos, Thoas LU and Johansson, Bertil LU (2009) In British Journal of Haematology 144. p.546-551
Abstract
Summary The t(X;7)(q22;q34), a translocation not previously reported in a neoplastic disorder, was identified and molecularly characterised in a paediatric T-cell acute lymphoblastic leukaemia (T-ALL), subsequently shown also to harbour a deletion of 6q, a STIL/TAL1 fusion and an activating NOTCH1 mutation. The t(X;7) was further investigated using fluorescence in situ hybridisation (FISH), real-time quantitative polymerase chain reaction (RQ-PCR) and Western blot analyses. FISH revealed a breakpoint at the T-cell receptor beta locus at 7q34 and mapped the corresponding breakpoint to Xq22.3. The latter region contains only two known genes, namely insulin receptor substrate 4 (IRS4) and collagen, type IV, alpha 5 (COL4A5), the expressions... (More)
Summary The t(X;7)(q22;q34), a translocation not previously reported in a neoplastic disorder, was identified and molecularly characterised in a paediatric T-cell acute lymphoblastic leukaemia (T-ALL), subsequently shown also to harbour a deletion of 6q, a STIL/TAL1 fusion and an activating NOTCH1 mutation. The t(X;7) was further investigated using fluorescence in situ hybridisation (FISH), real-time quantitative polymerase chain reaction (RQ-PCR) and Western blot analyses. FISH revealed a breakpoint at the T-cell receptor beta locus at 7q34 and mapped the corresponding breakpoint to Xq22.3. The latter region contains only two known genes, namely insulin receptor substrate 4 (IRS4) and collagen, type IV, alpha 5 (COL4A5), the expressions of which were analysed by the use of RQ-PCR. COL4A5 was not differentially expressed in the t(X;7)-positive sample compared to five T-ALL controls. However, a marked, 1000-fold overexpression of IRS4 was identified. Western blot analysis with a monoclonal antibody against IRS4 showed overexpression also at the protein level. Considering that forced expression of several members of the IRS family has been shown to result in increased cell proliferation, for example in haematopoietic cells, we hypothesise that the IRS4 up-regulation in T-ALL is pathogenetically important as a mitogenic stimulus. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
British Journal of Haematology
volume
144
pages
546 - 551
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000262635500010
  • pmid:19055661
  • scopus:58549112951
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2008.07453.x
language
English
LU publication?
yes
id
e009287e-0e07-4381-ba06-40e51b1ca30c (old id 1276466)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19055661?dopt=Abstract
date added to LUP
2009-01-09 09:15:56
date last changed
2017-01-01 07:37:44
@article{e009287e-0e07-4381-ba06-40e51b1ca30c,
  abstract     = {Summary The t(X;7)(q22;q34), a translocation not previously reported in a neoplastic disorder, was identified and molecularly characterised in a paediatric T-cell acute lymphoblastic leukaemia (T-ALL), subsequently shown also to harbour a deletion of 6q, a STIL/TAL1 fusion and an activating NOTCH1 mutation. The t(X;7) was further investigated using fluorescence in situ hybridisation (FISH), real-time quantitative polymerase chain reaction (RQ-PCR) and Western blot analyses. FISH revealed a breakpoint at the T-cell receptor beta locus at 7q34 and mapped the corresponding breakpoint to Xq22.3. The latter region contains only two known genes, namely insulin receptor substrate 4 (IRS4) and collagen, type IV, alpha 5 (COL4A5), the expressions of which were analysed by the use of RQ-PCR. COL4A5 was not differentially expressed in the t(X;7)-positive sample compared to five T-ALL controls. However, a marked, 1000-fold overexpression of IRS4 was identified. Western blot analysis with a monoclonal antibody against IRS4 showed overexpression also at the protein level. Considering that forced expression of several members of the IRS family has been shown to result in increased cell proliferation, for example in haematopoietic cells, we hypothesise that the IRS4 up-regulation in T-ALL is pathogenetically important as a mitogenic stimulus.},
  author       = {Karrman, Kristina and Kjeldsen, Eigil and Lassen, Carin and Isaksson, Margareth and Davidsson, Josef and Andersson, Anna and Hasle, Henrik and Fioretos, Thoas and Johansson, Bertil},
  issn         = {0007-1048},
  language     = {eng},
  pages        = {546--551},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {The t(X;7)(q22;q34) in paediatric T-cell acute lymphoblastic leukaemia results in overexpression of the insulin receptor substrate 4 gene through illegitimate recombination with the T-cell receptor beta locus.},
  url          = {http://dx.doi.org/10.1111/j.1365-2141.2008.07453.x},
  volume       = {144},
  year         = {2009},
}