Immunogenetic profiling in childhood acute lymphoblastic leukemia

Background: Much is known about prognostic implications of tumor DNA in cancer. Recent evidence indicates that an individual’s genetic makeup (genomic DNA) influences morbidity and mortality in many diseases. Associations with outcome in sepsis have been shown for polymorphic genes within the immune system, e.g. toll-like receptors and mannose-binding lectin within the innate immune system, and for both pro- and antiinflammatory cytokines (e.g. IL-6 and IL-10). We have earlier shown that infectious deaths comprise about two thirds of treatment related mortality in childhood acute lymphoblastic leukemia (ALL). Several risk factors for treatment related infections are known, such as neutropenia, use of steroids, central venous lines and nutritional status. The influence of immunogenetic variation on risk of infectious complications during treatment of ALL has not been throughly explored. Materials and methods: We will present our ongoing study on genetic polymorphisms which include about 240 target molecules within the immune system and related genes. Through bioinformatics several thousand single nucleotide polymorphisms (SNPs) have been selected for study. Our main purpose is to retrospectively identify an immunogenetic risk profile associated with severe infections in about 700 patients treated on the two last NOPHO ALL protocols (NOPHO ALL-92 and NOPHO ALL-2000 protocols). Genetic sequencing using high-throughput technology will take part during 2010. Possible future implications when integrating immunogenetics into more individualized treatment include use of prophylactic antibiotics during neutropenia and reduced treatment intensity for patients at high risk for sever infectious complications.