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Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol.

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Authors
Wolthers, B O
Frandsen, T L
Abrahamsson, J
Albertsen, B K
Helt, L R
Heyman, M
Jónsson, Ó G
Kõrgvee, L T
Lund, B
Raja, R A
Rasmussen, K K
Taskinen, M
Tulstrup, M
Vaitkevičienė, G E
Yadav, R
Gupta, R
Schmiegelow, K
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Issue Date
2017-02

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Citation
Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol. 2017, 31 (2):325-332 Leukemia
Abstract
Asparaginase (ASP)-associated pancreatitis (AAP) occurs during acute lymphoblastic leukemia treatment. Among 1285 children (1.0-17.9 years) diagnosed during July 2008-December 2014 and treated according to the Nordic/Baltic ALL2008 protocol, 86 (cumulative incidence=6.8%) developed AAP. Seventy-three cases were severe (diagnostic AAP criteria persisting >72 h) and 13 mild. Cases were older than controls (median: 6.5 vs 4.5 years; P=0.001). Pseudocysts developed in 28%. Of the 20 re-exposed to ASP, 9 (45%) developed a second AAP. After a median follow-up of 2.3 years, 8% needed permanent insulin therapy, and 7% had recurrent abdominal pain. Germline DNA on 62 cases and 638 controls was genotyped on Omni2.5exome-8-v1.2 BeadChip arrays. Overall, the ULK2 variant rs281366 showed the strongest association with AAP (P=5.8 × 10(-7); odds ratio (OR)=6.7). Cases with the rs281366 variant were younger (4.3 vs 8 years; P=0.015) and had lower risk of AAP-related complications (15% vs 43%; P=0.13) compared with cases without this variant. Among 45 cases and 517 controls <10 years, the strongest associations with AAP were found for RGS6 variant rs17179470 (P=9.8 × 10(-9); OR=7.3). Rs281366 is located in the ULK2 gene involved in autophagy, and RGS6 regulates G-protein signaling regulating cell dynamics. More than 50% of AAP cases <10 years carried one or both risk alleles.
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http://www.nature.com/leu/journal/v31/n2/full/leu2016203a.html
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Archived with thanks to Leukemia
ae974a485f413a2113503eed53cd6c53
10.1038/leu.2016.203
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English Journal Articles (Peer Reviewed)

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