Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia

Abstract

Acute lymphoblastic leukemia of pre-B cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/ resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest. Humans may inherit different numbers of the 6 distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to the development of B-ALL. We addressed this issue by performing a case-control study in Canadian children of white origin. Our results show that harboring activating KIR genes is associated with reduced risk for developing B-ALL in these children. Of the 6 activating KIR genes, KIR2DS2 was maximally associated with decreased risk for the disease (P ‫؍‬ 1.14 ؋ 10 ؊7 ). Furthermore, our results showed that inheritance of a higher number of activating KIR genes was associated with significant reductions in risk for ALL in children. These results were also consistent across different ALL phenotypes, which included children with pre-T cell ALL. Our study provides novel insights concerning the pathogenesis of childhood leukemia in white children and has implications for the development of new immunotherapies for this cancer. (Blood. 2011;118(5): 1323-1328)

Killer Cell Immunoglobulin-Like Receptor Genes Polymorphisms in Macedonian Patients with Haematological Malignancies

“…Although two recent studies reported higher frequency of activating KIR genes, such as KIR2DS1, KIR2DS3 and KIR2DS4 in patients with CML and ALL [22,23], we couldn't reproduce these findings in our cohort. Our findings are thus in agreement with those reported from Babor et al, who also found very similar frequencies of KIR genes among haematological patients and healthy controls with European origin [24].…”

Response: associations between activating KIR genes and childhood leukemia

“…1 Obviously, these results contradict those reported recently by us. 2 Interestingly, the frequencies of these genes in controls are more or less comparable in both studies. Babor and colleagues mentioned technical challenges associated with PCRbased KIR genotyping due to strong similarities between KIR genes and their many alleles.…”

New strategies for haploidentical transplantation

“…These observations are in line with a more recent case-control study including 109 children suffering from ALL. Almalte et al found that inheriting a higher number of activating KIR genes was associated with significant reduction in risk for development of ALL (66). These findings support the important influence of activating KIRs in pediatric ALL not only in the setting of haploidentical transplantation but also for the development and maybe the course and therapy of pediatric ALL.…”