Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from The Children's Oncology Group TARGET Project
Menée sur 45 patients pédiatriques atteints d'une leucémie lymphoblastique aiguë, cette étude n'identifie pas de mutation de gènes de tyrosine kinase à l'exception des mutations du gène JAK et d'une mutation du gène FLT3
One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1-like or Ph-like due to similarity of the gene expression profile (GEP) to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome. Prior studies demonstrated that about 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 GEP or other alterations suggestive of activated kinase signaling. Aside from JAK mutations and one 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.