Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project

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 IK...

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Bibliographic Details
Published in:	Blood Vol. 121; no. 3; p. 485
Main Authors:	Loh, Mignon L, Zhang, Jinghui, Harvey, Richard C, Roberts, Kathryn, Payne-Turner, Debbie, Kang, Huining, Wu, Gang, Chen, Xiang, Becksfort, Jared, Edmonson, Michael, Buetow, Kenneth H, Carroll, William L, Chen, I-Ming, Wood, Brent, Borowitz, Michael J, Devidas, Meenakshi, Gerhard, Daniela S, Bowman, Paul, Larsen, Eric, Winick, Naomi, Raetz, Elizabeth, Smith, Malcolm, Downing, James R, Willman, Cheryl L, Mullighan, Charles G, Hunger, Stephen P
Format:	Journal Article
Language:	English
Published:	United States 17.01.2013
Subjects:	Child Child, Preschool Disease-Free Survival Female fms-Like Tyrosine Kinase 3 - genetics fms-Like Tyrosine Kinase 3 - metabolism Gene Expression Regulation, Leukemic - physiology Humans Infant Janus Kinase 1 - genetics Janus Kinase 1 - metabolism Janus Kinase 2 - genetics Janus Kinase 2 - metabolism Male Neoplasm, Residual - enzymology Neoplasm, Residual - genetics Neoplasm, Residual - mortality Philadelphia Chromosome Precursor Cell Lymphoblastic Leukemia-Lymphoma - enzymology Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Receptors, Cytokine - genetics Receptors, Cytokine - metabolism Receptors, Purinergic P2Y - genetics Receptors, Purinergic P2Y - metabolism Signal Transduction - genetics Transcriptome
ISSN:	1528-0020, 1528-0020
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1528-0020 1528-0020
DOI:	10.1182/blood-2012-04-422691