ASH 2015
Comment: Genetic variants for increased risk of osteonecrosis in paediatric acute lymphocytic leukaemia identified
Dr Wendy Stock - University of Chicago, Chicago, USA
We’ve been listening to a very interesting talk from Dr Karol, Dr Seth Karol. He was talking about genetic risk factors for osteonecrosis in children with ALL and age was a factor and the age of 10 years was the issue. What was the big story there?
It’s very interesting. It’s well known, unfortunately, that young adults, young teenagers actually, have the highest risk of any population for osteonecrosis. It’s probably because of the developing and rapidly growing bone at that age that’s particularly sensitive to toxic agents. Variants that predispose to osteonecrosis have previously been identified in that age group but one of the things that this group did was really focus in on osteonecrosis in children under the age of 10 years. What they found was that they identified using a very, very large population of patients and a very unbiased approach using large genome sequencing using SNP arrays, they identified a number of variants that were associated with specific genes, particularly in the younger children, they also looked in the older children, the young adults, that were associated with bone development potentially and fat development within the bone.
What is the big story coming out of this? Things like glutamate receptor signalling was mentioned and also adipogenesis. So what, for you, is the big conclusion?
The big thing is that the types of predisposition factors, potentially, to the osteonecrosis problem may differ in younger versus older children. The ones in younger children may have to do a lot with intrinsic bone formation whereas the ones in older children potentially have to do more with vascular supply to the bone. So those are two of the differences. Also these variants that were described are brand new variants that have never previously been described and give you some idea of things that potentially could be used to modulate that problem in the population of patients that has inherited those risk factors as predisposing factors to osteonecrosis.
And the take-home for you for clinicians from this would be what?
I think that the take-home message is that as we are allowed to screen and identify risk variants we’re going to be able to more carefully identify patients who are at risk for these very severe complications of our very successful treatments and that perhaps knowing these things in advance may allow us to modulate treatment in the future to avoid the complications of osteonecrosis. Most importantly, it also gives us ideas about how therapeutically, since the drugs that we use are very important for the treatment, how we might, based on the genetic information that we’ve obtained, use things to inhibit the process that was identified by the aberrant genes that are involved in the development of these problems in the bone.
