Expression analysis and characterization of alternatively spliced transcripts of human IL-7r alpha chain encoding two truncated receptor proteins in relapsed childhood ALL

In the family of cytokines and cytokine receptors, alternative splicing of pre-mRNA is a frequently observed process that generates different protein isoforms from a single genetic locus. The splicing-derived cytokine recepto r protein isoforms are mostly soluble receptors or show alterations in thei r cytoplasmic domain. It is possible that receptor abnormalities or a patho logical ratio of different isoforms may contribute to leukaemia by circumve nting normal growth factor control or altering the balance of proliferation and differentiation. IL-7 plays a critical role in early stages of both B and T cell maturation. Moreover, it stimulates the expansion of mature T ce lls including anti-tumour reactive cells as well as a number of T and B cel l malignancies underlining its potential importance for deregulated lymphoi d proliferation and leukaemogenesis, Here, we present detailed data on the expression of the interleukin 7 receptor a chain (IL-7R alpha) in leukaemic cells from 210 children with acute lymphoblastic leukaemia (ALL) and descr ibe two novel alternatively spliced transcripts of human IL-7R alpha coding for truncated receptor proteins which are still capable of binding IL-7, I L-7R alpha mRNA expression was more frequent in more mature pre-Il ALL [91% (30/33)] than in common [81% (811100)] or pro-B ALL [64% (18/28)], or even in T ALL [64% (29/45)], These results are in concordance with flow cytomet ric analyses on the proportion of IL-7Ra bearing cells among total blast ce ll population. Our results lead us to assume that splicing derived IL-7Ra i soforms play a potential role in modulating IL-7 signal transduction and mi ght be important for the pathogenesis of leukaemia. (C) 2000 Academic Press .