TY - JOUR
T1 - Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients
T2 - a report from the children’s oncology group
AU - Roberts, Kathryn G.
AU - Reshmi, Shalini C.
AU - Harvey, Richard C.
AU - Chen, I. Ming
AU - Patel, Kinnari
AU - Stonerock, Eileen
AU - Jenkins, Heather
AU - Dai, Yunfeng
AU - Valentine, Marc
AU - Gu, Zhaohui
AU - Zhao, Yaqi
AU - Zhang, Jinghui
AU - Payne-Turner, Debbie
AU - Devidas, Meenakshi
AU - Heerema, Nyla A.
AU - Carroll, Andrew J.
AU - Raetz, Elizabeth A.
AU - Borowitz, Michael J.
AU - Wood, Brent L.
AU - Mattano, Leonard A.
AU - Maloney, Kelly W.
AU - Carroll, William L.
AU - Loh, Mignon L.
AU - Willman, Cheryl L.
AU - Gastier-Foster, Julie M.
AU - Mullighan, Charles G.
AU - Hunger, Stephen P.
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/8/23
Y1 - 2018/8/23
N2 - Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL; BCR-ABL1–like ALL) in children with National Cancer Institute (NCI) intermediate- or high-risk (HR) ALL 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. The prevalence, outcome, and potential for targeted therapy of Ph-like ALL in standard-risk (SR) ALL is less clear. We retrospectively analyzed a cohort of 1023 SR childhood B-ALL consecutively enrolled in the Children’s Oncology Group AALL0331 clinical trial. The Ph-like ALL gene expression profile was identified in 206 patients, and 67 patients with either BCR-ABL1 (n 5 6) or ETV6-RUNX1 (n 5 61) were excluded from downstream analysis, leaving 139 of 1023 (13.6%) as Ph-like. Targeted reverse transcription polymerase chain reaction 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 with non–Ph-like ALL (82.4 6 3.6% vs 90.7 6 1.0%, P 5 .0022), with no difference in overall survival (93.2 6 2.4% vs 95.8 6 0.7%, P 5 .14).with approved kinase inhibitors are less frequent in SR than in HR ALL.
AB - Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL; BCR-ABL1–like ALL) in children with National Cancer Institute (NCI) intermediate- or high-risk (HR) ALL 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. The prevalence, outcome, and potential for targeted therapy of Ph-like ALL in standard-risk (SR) ALL is less clear. We retrospectively analyzed a cohort of 1023 SR childhood B-ALL consecutively enrolled in the Children’s Oncology Group AALL0331 clinical trial. The Ph-like ALL gene expression profile was identified in 206 patients, and 67 patients with either BCR-ABL1 (n 5 6) or ETV6-RUNX1 (n 5 61) were excluded from downstream analysis, leaving 139 of 1023 (13.6%) as Ph-like. Targeted reverse transcription polymerase chain reaction 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 with non–Ph-like ALL (82.4 6 3.6% vs 90.7 6 1.0%, P 5 .0022), with no difference in overall survival (93.2 6 2.4% vs 95.8 6 0.7%, P 5 .14).with approved kinase inhibitors are less frequent in SR than in HR ALL.
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U2 - 10.1182/blood-2018-04-841676
DO - 10.1182/blood-2018-04-841676
M3 - Article
C2 - 29997224
AN - SCOPUS:85052111502
SN - 0006-4971
VL - 132
SP - 815
EP - 824
JO - Blood
JF - Blood
IS - 8
ER -