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. 2016 Sep;30(9):1959-62.
doi: 10.1038/leu.2016.116. Epub 2016 May 12.

LMO2 and IL2RG synergize in thymocytes to mimic the evolution of SCID-X1 gene therapy-associated T-cell leukaemia

K Ruggero  1 , O Al-Assar  1 , J S Chambers  1 , R Codrington  1   2 , T Brend  1 , T H Rabbitts  1
Affiliations

LMO2 and IL2RG synergize in thymocytes to mimic the evolution of SCID-X1 gene therapy-associated T-cell leukaemia

K Ruggero et al. Leukemia. 2016 Sep.
No abstract available

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Figures

Figure 1
Figure 1
T-cell tumours in Lck-Lmo2 and Lck-Lmo2; Lck-IL2RG transgenic mice. (a) Transgenic mice were made expressing Lmo2 and/or IL2RG in thymocytes. Cohorts of mice expressing either LMO2 or IL2RG or both transgenes were monitored over an 18-month period, and disease assessed by macroscopic changes to habit and subsequent post-mortem. (b) Kaplan–Meier comparison of disease incidence. The Lmo2 and IL2RG double transgenic (n=21) group developed T-cell neoplasia at an accelerated rate compared with single Lmo2 transgenic mice (P-value <0.0001) (n=22). Single IL2RG mice did not develop tumours (n=22). (c-f) Flow cytometry of CD4, CD8, CD25 and CD44 of a wild-type C57Bl6 mouse (male; 21 weeks) (c) secondary tumours derived from the spleen of Rag1 null recipient mice transplanted with Lck-Lmo2 STG1 (d) Lck-Lmo2; Lck-IL2RG DTG21 (e) or Lck-Lmo2; Lck-IL2RG DTG22 (f) primary tumours. Cells were gated on CD90.2-positive population.
Figure 2
Figure 2
Notch1 mutations in transgenic tumours. Genomic DNA from thymoma samples were analysed by MCA for potential Notch1 mutations at exon 26, 27 and 34 regions. Positive samples were sequenced across the appropriate exon regions. Mutated amino acids are shown in bold. Point mutations occur in exons 26 and 27 (a), except one Lck-Lmo2; Lck-IL2RG tumour that has a frame shift in exon 26. Exon 34 (b) changes result in frame shifts.
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References

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