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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1276466
- author
- 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
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Haematology
- volume
- 144
- pages
- 546 - 551
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000262635500010
- pmid:19055661
- scopus:58549112951
- pmid:19055661
- 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
- 2016-04-04 08:36:35
- date last changed
- 2022-08-23 04:23:51
@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 = {{Wiley-Blackwell}},
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}},
doi = {{10.1111/j.1365-2141.2008.07453.x}},
volume = {{144}},
year = {{2009}},
}