Overexpression of the Ikaros 6 isoform is restricted to t(4;11) acute lymphoblastic leukaemia in children and infants and has a role in B-cell survival.
The Ikaros transcription factor has been shown to play an important role in the differentiation of both myeloid and lymphoid lineages. Mice heterozygous for a dominant negative (DN) ikaros isoform develop T-cell leukaemia and lymphoma with 100% penetrance. Overexpression of DN Ikaros isoforms has been reported in some forms of leukaemia, such as childhood acute myelomonocytic and monocytic leukaemias, adult B-cell acute lymphoblastic leukaemias (B ALL) and in childhood and adult pre-B ALL. In this study, the expression of Ikaros isoforms in 49 infant and childhood leukaemia patients was analysed by reverse transcription polymerase chain reaction and Western blot analysis. We found overexpression of the DN Ikaros 6 (Ik6) isoform in a subset of leukaemia patients harbouring t(4;11) translocations. To further study the consequences of Ik6 overexpression in B ALL, we inducibly expressed Ik6 in BaF3 cells and found that Ik6 overexpression delayed cell death after interleukin-3 withdrawal, suggesting that overexpression of Ik6 found in t(4;11) B cells could contribute to leukaemogenesis by preventing the apoptosis of cells in an environment with reduced survival factors.
Ruiz
Anna
A
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, London, UK.
Jiang
Jie
J
Kempski
Helena
H
Brady
Hugh J M
HJ
D001402:B-Lymphocytes / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D051740:Ikaros Transcription Factor; D007223:Infant; D007377:Interleukin-3 / Q000502:physiology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D007377:Interleukin-3; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D051740:Ikaros Transcription Factor