Paediatric NEWS & NOTES from the 50th annual ASH meeting

Abstract

The report summarizes several lectures that proved particularly notable for paediatric haematologists at the ASH meeting 2008. Neal S. Young (NIH, Bethesda, U.S.A.) illustrated his findings about the frequent impact of telomere shortening caused by mutations in the telomerase complex in the pathogenesis of severe aplastic anaemia (SAA). The presence of these mutations also has therapeutic implications, as carriers are at risk to respond poorly to immunosuppressive treatment regimens. The relevance of genome wide analysis of DNA copy number alterations (CNA) for the risk stratification in paediatric B-precursor ALL was demonstrated by Charles G. Mullighan (St. Judes Hospital, Memphis, U.S.A.). Mutations occurring in a number of genes that regulate lymphoid development (like IKZF-1) were identified as predictors of poor outcome. Furthermore, the evaluation of CNA in diagnostic and relapse samples of ALL patients allows to retrace the clonal evolution of the disease. Lyndal Kearney (Institute of Cancer Research, London, U.K.) reported on new insights into leukaemogenesis gained by comparing several identical twin-pairs with concordant TEL-AML1 positive B-precursor ALL. The results of single nucleotide polymorphism (SNP) arrays illustrate how pre-leukaemic, TEL-AML1 positive clones convert into overt ALL by acquiring secondary functional mutations. Defective apoptosis accounts for abnormal lymphocyte survival and autoimmune processes in autoimmune lymphoproliferative disease (ALPS). Stephan Grupp and David T. Teachey (Children’s Hospital, Philadelphia, U.S.A.) successfully applied the signal transduction inhibitor rapamycin to induce lymphocyte apoptosis in ALPS patients. Considerable clinical improvements were achieved in each of the patients treated in a phase I/II trial.