TY - JOUR
T1 - Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia
T2 - A report from the Children's Oncology Group TARGET Project
AU - Loh, Mignon L.
AU - Zhang, Jinghui
AU - Harvey, Richard C.
AU - Roberts, Kathryn
AU - Payne-Turner, Debbie
AU - Kang, Huining
AU - Wu, Gang
AU - Chen, Xiang
AU - Becksfort, Jared
AU - Edmonson, Michael
AU - Buetow, Kenneth H.
AU - Carroll, William L.
AU - Chen, I. Ming
AU - Wood, Brent
AU - Borowitz, Michael J.
AU - Devidas, Meenakshi
AU - Gerhard, Daniela S.
AU - Bowman, Paul
AU - Larsen, Eric
AU - Winick, Naomi
AU - Raetz, Elizabeth
AU - Smith, Malcolm
AU - Downing, James R.
AU - Willman, Cheryl L.
AU - Mullighan, Charles G.
AU - Hunger, Stephen P.
PY - 2013/1/17
Y1 - 2013/1/17
N2 - One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1-like or Ph-like because of similarity of the gene expression profile to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome. Prior studies demonstrated that approximately half of these patients had genomic lesions leading to CRLF2 overexpression, with half of such cases harboring somatic mutations in the Janus kinases JAK1 and JAK2. To determine whether mutations in other tyrosine kinases might also occur in ALL, we sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with either a Ph-like gene expression profile or other alterations suggestive of activated kinase signaling. Aside from JAK mutations and 1 FLT3 mutation, no somatic mutations were found in any other tyrosine kinases, suggesting that alternative mechanisms are responsible for activated kinase signaling in high-risk ALL. Copyright 2011 by The American Society of Hematology; all rights reserved.
AB - One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1-like or Ph-like because of similarity of the gene expression profile to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome. Prior studies demonstrated that approximately half of these patients had genomic lesions leading to CRLF2 overexpression, with half of such cases harboring somatic mutations in the Janus kinases JAK1 and JAK2. To determine whether mutations in other tyrosine kinases might also occur in ALL, we sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with either a Ph-like gene expression profile or other alterations suggestive of activated kinase signaling. Aside from JAK mutations and 1 FLT3 mutation, no somatic mutations were found in any other tyrosine kinases, suggesting that alternative mechanisms are responsible for activated kinase signaling in high-risk ALL. Copyright 2011 by The American Society of Hematology; all rights reserved.
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U2 - 10.1182/blood-2012-04-422691
DO - 10.1182/blood-2012-04-422691
M3 - Article
C2 - 23212523
AN - SCOPUS:84872457525
SN - 0006-4971
VL - 121
SP - 485
EP - 488
JO - Blood
JF - Blood
IS - 3
ER -