{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Reshmi SC"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["3352-3361"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5482101"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["129(25)"],"pubmed_abstract":["Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed patients with childhood B-lineage ALL with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of whom were excluded from additional analyses because of the presence of <i>BCR</i>-<i>ABL1</i> (n = 46) or <i>ETV6</i>-<i>RUNX1</i> (n = 11). Among the remaining 284 patients (20.4%), overexpression and rearrangement of <i>CRLF2</i> (<i>IGH</i>-<i>CRLF2</i> or <i>P2RY8</i>-<i>CRLF2</i>) were identified in 124 (43.7%), with concomitant genomic alterations activating the JAK-STAT pathway (<i>JAK1</i>, <i>JAK2</i>, <i>IL7R</i>) identified in 63 patients (50.8% of those with <i>CRLF2</i> rearrangement). Among the remaining patients, using reverse transcriptase polymerase chain reaction or transcriptome sequencing, we identified targetable ABL-class fusions (<i>ABL1</i>, <i>ABL2</i>, <i>CSF1R</i>, and <i>PDGFRB</i>) in 14.1%, <i>EPOR</i> rearrangements or <i>JAK2</i> fusions in 8.8%, alterations activating other JAK-STAT signaling genes (<i>IL7R</i>, <i>SH2B3</i>, <i>JAK1</i>) in 6.3% or other kinases (<i>FLT3</i>, <i>NTRK3</i>, <i>LYN</i>) in 4.6%, and mutations involving the Ras pathway (<i>KRAS</i>, <i>NRAS</i>, <i>NF1</i>, <i>PTPN11</i>) in 6% of those with Ph-like ALL. We identified 8 new rearrangement partners for 4 kinase genes previously reported to be rearranged in Ph-like ALL. The current findings provide support for the precision-medicine testing and treatment approach for Ph-like ALL implemented in Children's Oncology Group ALL trials."],"journal":["Blood"],"pubmed_title":["Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group."],"pmcid":["PMC5482101"],"funding_grant_id":["P30 CA016058","P50 GM115279","P30 CA021765","U10 CA180886","U10 CA180899"],"pubmed_authors":["Burke MJ","Zhang J","Loh ML","Stonerock E","Borowitz MJ","Dai Y","Heerema NA","Wood BL","Devidas M","Raetz EA","Roberts KG","Liu Y","Willman CL","Shao Y","Hunger SP","Harvey RC","Gastier-Foster JM","Angiolillo AL","Jenkins H","Carroll WL","Smith A","Easton J","Zweidler-McKay PA","Gu Z","Chen IM","Nguyen JV","Payne-Turner D","Li Y","Tran TH","Carroll AJ","Mullighan CG","Salzer WL","Reshmi SC","Valentine M","Rabin KR"],"additional_accession":[]},"is_claimable":false,"name":"Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group.","description":"Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype characterized by genomic alterations that activate cytokine receptor and kinase signaling. We examined the frequency and spectrum of targetable genetic lesions in a retrospective cohort of 1389 consecutively diagnosed patients with childhood B-lineage ALL with high-risk clinical features and/or elevated minimal residual disease at the end of remission induction therapy. The Ph-like gene expression profile was identified in 341 of 1389 patients, 57 of whom were excluded from additional analyses because of the presence of <i>BCR</i>-<i>ABL1</i> (n = 46) or <i>ETV6</i>-<i>RUNX1</i> (n = 11). Among the remaining 284 patients (20.4%), overexpression and rearrangement of <i>CRLF2</i> (<i>IGH</i>-<i>CRLF2</i> or <i>P2RY8</i>-<i>CRLF2</i>) were identified in 124 (43.7%), with concomitant genomic alterations activating the JAK-STAT pathway (<i>JAK1</i>, <i>JAK2</i>, <i>IL7R</i>) identified in 63 patients (50.8% of those with <i>CRLF2</i> rearrangement). Among the remaining patients, using reverse transcriptase polymerase chain reaction or transcriptome sequencing, we identified targetable ABL-class fusions (<i>ABL1</i>, <i>ABL2</i>, <i>CSF1R</i>, and <i>PDGFRB</i>) in 14.1%, <i>EPOR</i> rearrangements or <i>JAK2</i> fusions in 8.8%, alterations activating other JAK-STAT signaling genes (<i>IL7R</i>, <i>SH2B3</i>, <i>JAK1</i>) in 6.3% or other kinases (<i>FLT3</i>, <i>NTRK3</i>, <i>LYN</i>) in 4.6%, and mutations involving the Ras pathway (<i>KRAS</i>, <i>NRAS</i>, <i>NF1</i>, <i>PTPN11</i>) in 6% of those with Ph-like ALL. We identified 8 new rearrangement partners for 4 kinase genes previously reported to be rearranged in Ph-like ALL. The current findings provide support for the precision-medicine testing and treatment approach for Ph-like ALL implemented in Children's Oncology Group ALL trials.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Jun","modification":"2024-11-12T03:26:44.708Z","creation":"2019-03-26T23:42:00Z"},"accession":"S-EPMC5482101","cross_references":{"pubmed":["28408464"],"doi":["10.1182/blood-2016-12-758979"]}}