作者
Jonathan Paolino, Boris Dimitrov, Beth Apsel Winger, Angelica Sandoval-Perez, Amith Vikram Rangarajan, Nicole Ocasio-Martinez, Harrison K Tsai, Yuting Li, Amanda L Robichaud, Delan Khalid, Charlie Hatton, Riaz Gillani, Petri Polonen, Anthony Dilig, Giacomo Gotti, Julia Kavanagh, Asmani A Adhav, Sean Gow, Jonathan Tsai, Yen Der Li, Benjamin L Ebert, Eliezer M Van Allen, Jacob Bledsoe, Annette S Kim, Sarah K Tasian, Stacy L Cooper, Todd M Cooper, Nobuko Hijiya, Maria Luisa Sulis, Neerav N Shukla, Jeffrey A Magee, Charles G Mullighan, Michael J Burke, Marlise R Luskin, Brenton G Mar, Matthew P Jacobson, Marian H Harris, Kimberly Stegmaier, Andrew E Place, Yana Pikman
发表日期
2023/11/14
期刊
Clinical Cancer Research
卷号
29
期号
22
页码范围
4613-4626
出版商
American Association for Cancer Research
简介
Purpose
Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have limited therapeutic options. Clinical use of genomic profiling provides an opportunity to identify targetable alterations to inform therapy.
Experimental Design
We describe a cohort of 14 pediatric patients with relapsed or refractory T-ALL enrolled on the Leukemia Precision-based Therapy (LEAP) Consortium trial (NCT02670525) and a patient with T-LBL, discovering alterations in platelet-derived growth factor receptor-α (PDGFRA) in 3 of these patients. We identified a novel mutation in PDGFRA, p.D842N, and used an integrated structural modeling and molecular biology approach to characterize mutations at D842 to guide therapeutic targeting. We conducted a preclinical study of avapritinib in a mouse patient-derived xenograft (PDX) model of …
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J Paolino, B Dimitrov, B Apsel Winger… - Clinical Cancer Research, 2023