Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia

Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia


Karol SE, (2016). Blood. (Link to abstract)


This analysis looks at genetic risk factors for osteonecrosis in patients with ALL, which is a major toxicity with long-term morbidity in patients undergoing treatment for ALL. Age >10 years is a well-known risk factor, but 40% of children affected by osteonecrosis are <10 years. This article evaluated the germline genotype by using whole exome sequencing of 369 patients <10 years with 82 being affected with osteonecrosis. Variants close to three genes (BMP7, PROX1-AS1, and GRID2) were identified as risk factors. Please see as well a previous article from this author looking at genetic risk factors for osteonecrosis in patients with ALL in a cohort of patients from pediatric treatment protocols in Blood. A SNP in the glutamate receptor GRIN3A locus was identified as a risk factor for osteonecrosis (Karol SE, et al. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood. 2015;126(15):1770–1776). Interestingly, the mutation previously identified in a mixed cohort of patients <10y AND >10 years did not show up as a risk factor in this cohort of patients exclusively <10 years.



* According to this and other studies, there are genetic risk factors to develop osteonecrosis when undergoing treatment for ALL. It is too early to include this knowledge to assess the risk of developing this complication. Furthermore, it is unclear what impact this knowledge could have on treatment (modification of steroids?).