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Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report. / Wolthers, Benjamin O.; Frandsen, Thomas L.; Patel, Chirag J; Abaji, Rachid; Attarbaschi, Andishe; Barzilai, Shlomit; Colombini, Antonella; Escherich, Gabriele; Grosjean, Marie; Krajinovic, Maja; Larsen, Eric; Liang, Der-Cherng; Möricke, Anja; Rasmussen, Kirsten K.; Samarasinghe, Sujith; Silverman, Lewis B.; van der Sluis, Inge M.; Stanulla, Martin; Tulstrup, Morten; Yadav, Rachita; Yang, Wenjian; Zapotocka, Ester; Gupta, Ramneek; Schmiegelow, Kjeld.

In: Haematologica, Vol. 104, No. 3, 2019, p. 556-563.

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

Harvard

Wolthers, BO, Frandsen, TL, Patel, CJ, Abaji, R, Attarbaschi, A, Barzilai, S, Colombini, A, Escherich, G, Grosjean, M, Krajinovic, M, Larsen, E, Liang, D-C, Möricke, A, Rasmussen, KK, Samarasinghe, S, Silverman, LB, van der Sluis, IM, Stanulla, M, Tulstrup, M, Yadav, R, Yang, W, Zapotocka, E, Gupta, R & Schmiegelow, K 2019, 'Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report', Haematologica, vol. 104, no. 3, pp. 556-563. https://doi.org/10.3324/haematol.2018.199356

APA

CBE

Wolthers BO, Frandsen TL, Patel CJ, Abaji R, Attarbaschi A, Barzilai S, Colombini A, Escherich G, Grosjean M, Krajinovic M, Larsen E, Liang D-C, Möricke A, Rasmussen KK, Samarasinghe S, Silverman LB, van der Sluis IM, Stanulla M, Tulstrup M, Yadav R, Yang W, Zapotocka E, Gupta R, Schmiegelow K. 2019. Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report. Haematologica. 104(3):556-563. https://doi.org/10.3324/haematol.2018.199356

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Author

Wolthers, Benjamin O. ; Frandsen, Thomas L. ; Patel, Chirag J ; Abaji, Rachid ; Attarbaschi, Andishe ; Barzilai, Shlomit ; Colombini, Antonella ; Escherich, Gabriele ; Grosjean, Marie ; Krajinovic, Maja ; Larsen, Eric ; Liang, Der-Cherng ; Möricke, Anja ; Rasmussen, Kirsten K. ; Samarasinghe, Sujith ; Silverman, Lewis B. ; van der Sluis, Inge M. ; Stanulla, Martin ; Tulstrup, Morten ; Yadav, Rachita ; Yang, Wenjian ; Zapotocka, Ester ; Gupta, Ramneek ; Schmiegelow, Kjeld. / Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report. In: Haematologica. 2019 ; Vol. 104, No. 3. pp. 556-563.

Bibtex

@article{919c3620deb3409ba4483146849bbee3,
title = "Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report",
abstract = "Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten acute lymphoblastic leukemia trial groups contributed remission samples from patients aged 1.0-17.9 years and treated from 2000-2016. Cases were defined (n=244) by at least two of the following criteria: i) abdominal pain, ii) pancreatic enzymes >3 x upper normal limit, iii) imaging compatible with asparaginase-associated pancreatitis. Controls (n=1320) completed intended asparaginase therapy, 78{\%} receiving ≥8 pegylated-asparaginase injections, without developing aparaginase-associated pancreatitis. rs62228256 on 20q13.2 showed the strongest association (OR=3.75; P=5.2x10-8). Moreover, rs13228878 (OR=0.61; P=7.1x10-6) and rs10273639 (OR=0.62; P=1.1x10-5) on 7q34 showed significant association. A Dana Farber Cancer Institute ALL Consortium cohort consisting of patients treated protocols from 1987-2004 (controls=285, cases=33), and the Children's Oncology Group AALL0232 cohort (controls=2653, cases=76) were available as replication cohorts for the 20q13.2 and 7q34 variants, respectively. While rs62228256 was not validated (P=0.86), both rs13228878 (P=0.03) and rs10273639 (P=0.04) were. rs13228878 and rs10273639 are in high linkage disequilibrium (r2=0.94) and associated with elevated expression of the trypsinogen encoding PRSS1 gene and are known risk variants for alcohol-associated and sporadic pancreatitis in adults. Intra-pancreatic trypsinogen cleavage to proteolytic trypsin induces autodigestion and pancreatitis. Asparaginase-associated pancreatitis and non-asparaginase associated pancreatitis shares genetic predisposition and targeting the trypsinogen activation pathway may enable identification of effective interventions towards asparaginase-associated pancreatitis.",
author = "Wolthers, {Benjamin O.} and Frandsen, {Thomas L.} and Patel, {Chirag J} and Rachid Abaji and Andishe Attarbaschi and Shlomit Barzilai and Antonella Colombini and Gabriele Escherich and Marie Grosjean and Maja Krajinovic and Eric Larsen and Der-Cherng Liang and Anja M{\"o}ricke and Rasmussen, {Kirsten K.} and Sujith Samarasinghe and Silverman, {Lewis B.} and {van der Sluis}, {Inge M.} and Martin Stanulla and Morten Tulstrup and Rachita Yadav and Wenjian Yang and Ester Zapotocka and Ramneek Gupta and Kjeld Schmiegelow",
year = "2019",
doi = "10.3324/haematol.2018.199356",
language = "English",
volume = "104",
pages = "556--563",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "3",

}

RIS

TY - JOUR

T1 - Trypsin encoding PRSS1-PRSS2 variation influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report

AU - Wolthers, Benjamin O.

AU - Frandsen, Thomas L.

AU - Patel, Chirag J

AU - Abaji, Rachid

AU - Attarbaschi, Andishe

AU - Barzilai, Shlomit

AU - Colombini, Antonella

AU - Escherich, Gabriele

AU - Grosjean, Marie

AU - Krajinovic, Maja

AU - Larsen, Eric

AU - Liang, Der-Cherng

AU - Möricke, Anja

AU - Rasmussen, Kirsten K.

AU - Samarasinghe, Sujith

AU - Silverman, Lewis B.

AU - van der Sluis, Inge M.

AU - Stanulla, Martin

AU - Tulstrup, Morten

AU - Yadav, Rachita

AU - Yang, Wenjian

AU - Zapotocka, Ester

AU - Gupta, Ramneek

AU - Schmiegelow, Kjeld

PY - 2019

Y1 - 2019

N2 - Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten acute lymphoblastic leukemia trial groups contributed remission samples from patients aged 1.0-17.9 years and treated from 2000-2016. Cases were defined (n=244) by at least two of the following criteria: i) abdominal pain, ii) pancreatic enzymes >3 x upper normal limit, iii) imaging compatible with asparaginase-associated pancreatitis. Controls (n=1320) completed intended asparaginase therapy, 78% receiving ≥8 pegylated-asparaginase injections, without developing aparaginase-associated pancreatitis. rs62228256 on 20q13.2 showed the strongest association (OR=3.75; P=5.2x10-8). Moreover, rs13228878 (OR=0.61; P=7.1x10-6) and rs10273639 (OR=0.62; P=1.1x10-5) on 7q34 showed significant association. A Dana Farber Cancer Institute ALL Consortium cohort consisting of patients treated protocols from 1987-2004 (controls=285, cases=33), and the Children's Oncology Group AALL0232 cohort (controls=2653, cases=76) were available as replication cohorts for the 20q13.2 and 7q34 variants, respectively. While rs62228256 was not validated (P=0.86), both rs13228878 (P=0.03) and rs10273639 (P=0.04) were. rs13228878 and rs10273639 are in high linkage disequilibrium (r2=0.94) and associated with elevated expression of the trypsinogen encoding PRSS1 gene and are known risk variants for alcohol-associated and sporadic pancreatitis in adults. Intra-pancreatic trypsinogen cleavage to proteolytic trypsin induces autodigestion and pancreatitis. Asparaginase-associated pancreatitis and non-asparaginase associated pancreatitis shares genetic predisposition and targeting the trypsinogen activation pathway may enable identification of effective interventions towards asparaginase-associated pancreatitis.

AB - Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten acute lymphoblastic leukemia trial groups contributed remission samples from patients aged 1.0-17.9 years and treated from 2000-2016. Cases were defined (n=244) by at least two of the following criteria: i) abdominal pain, ii) pancreatic enzymes >3 x upper normal limit, iii) imaging compatible with asparaginase-associated pancreatitis. Controls (n=1320) completed intended asparaginase therapy, 78% receiving ≥8 pegylated-asparaginase injections, without developing aparaginase-associated pancreatitis. rs62228256 on 20q13.2 showed the strongest association (OR=3.75; P=5.2x10-8). Moreover, rs13228878 (OR=0.61; P=7.1x10-6) and rs10273639 (OR=0.62; P=1.1x10-5) on 7q34 showed significant association. A Dana Farber Cancer Institute ALL Consortium cohort consisting of patients treated protocols from 1987-2004 (controls=285, cases=33), and the Children's Oncology Group AALL0232 cohort (controls=2653, cases=76) were available as replication cohorts for the 20q13.2 and 7q34 variants, respectively. While rs62228256 was not validated (P=0.86), both rs13228878 (P=0.03) and rs10273639 (P=0.04) were. rs13228878 and rs10273639 are in high linkage disequilibrium (r2=0.94) and associated with elevated expression of the trypsinogen encoding PRSS1 gene and are known risk variants for alcohol-associated and sporadic pancreatitis in adults. Intra-pancreatic trypsinogen cleavage to proteolytic trypsin induces autodigestion and pancreatitis. Asparaginase-associated pancreatitis and non-asparaginase associated pancreatitis shares genetic predisposition and targeting the trypsinogen activation pathway may enable identification of effective interventions towards asparaginase-associated pancreatitis.

U2 - 10.3324/haematol.2018.199356

DO - 10.3324/haematol.2018.199356

M3 - Journal article

VL - 104

SP - 556

EP - 563

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 3

ER -