Title |
Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group
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Published in |
Blood, July 2018
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DOI | 10.1182/blood-2018-04-841676 |
Pubmed ID | |
Authors |
Kathryn G Roberts, Shalini C Reshmi, Richard C Harvey, I-Ming Chen, Kinnari Patel, Eileen Stonerock, Heather Jenkins, Yunfeng Dai, Marc Valentine, Zhaohui Gu, Yaqi Zhao, Jinghui Zhang, Debbie Payne-Turner, Meenakshi Devidas, Nyla A Heerema, Andrew J Carroll, Elizabeth A Raetz, Michael J Borowitz, Brent L Wood, Leonard A Mattano, Kelly W Maloney, William L Carroll, Mignon L Loh, Cheryl L Willman, Julie M Gastier-Foster, Charles G Mullighan, Stephen P Hunger |
Abstract |
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL; BCR-ABL1-like ALL) in children with NCI high-risk (HR) ALL as defined by age and initial white blood cell count, or intermediate risk as defined by minimal residual disease response, is associated with poor outcome. Ph-like ALL is characterized by genetic alterations that activate cytokine receptor and kinase signaling and may be amenable to treatment with tyrosine kinase inhibitors (TKIs). The prevalence, outcome and potential for targeted therapy of Ph-like ALL in NCI standard-risk (SR) ALL is less clear. We retrospectively analyzed a cohort of 1023 SR childhood B-ALL consecutively enrolled on the Children's Oncology Group AALL0331 clinical trial. The Ph-like ALL gene expression profile was identified in 206 patients, 67 patients with either BCR-ABL1 (n=6) or ETV6-RUNX1 (n=61) were excluded from downstream analysis, leaving 139 of 1023 (13.6%) as Ph-like. Targeted RT-PCR assays and RNA-sequencing identified kinase-activating alterations in 38.8% of SR Ph-like cases, including CRLF2 rearrangements (29.5% of Ph-like), ABL-class fusions (1.4%), JAK2 fusions (1.4%), an NTRK3 fusion (0.7%) and other sequence mutations (IL7R, KRAS, NRAS; 5.6%). Patients with Ph-like ALL had inferior 7-year event-free survival compared to non Ph-like ALL (82.4±3.6% vs. 90.7±1.0%, P = .0022), with no difference in overall survival (93.2±2.4% vs. 95.8±0.7%, P = .14). These findings illustrate the significant differences in the spectrum of kinase alterations and clinical outcome of Ph-like ALL based on presenting clinical features, and establish that genomic alterations potentially targetable with approved kinase inhibitors are less frequent in SR than in HR ALL. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 8 | 38% |
United Kingdom | 2 | 10% |
Japan | 1 | 5% |
France | 1 | 5% |
Saudi Arabia | 1 | 5% |
Turkey | 1 | 5% |
Unknown | 7 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 9 | 43% |
Members of the public | 6 | 29% |
Scientists | 4 | 19% |
Science communicators (journalists, bloggers, editors) | 2 | 10% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 89 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Other | 13 | 15% |
Researcher | 13 | 15% |
Student > Ph. D. Student | 8 | 9% |
Student > Postgraduate | 8 | 9% |
Student > Doctoral Student | 7 | 8% |
Other | 16 | 18% |
Unknown | 24 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 35 | 39% |
Biochemistry, Genetics and Molecular Biology | 15 | 17% |
Agricultural and Biological Sciences | 5 | 6% |
Unspecified | 1 | 1% |
Immunology and Microbiology | 1 | 1% |
Other | 3 | 3% |
Unknown | 29 | 33% |