Case Report: Precision Medicine Target Revealed by In Vitro Modeling of Relapsed, Refractory Acute Lymphoblastic Leukemia From a Child With Neurofibromatosis
Date
2022
Authors
Heatley, S.L.
Page, E.C.
Eadie, L.N.
McClure, B.J.
Rehn, J.
Yeung, D.T.
Osborn, M.
Revesz, T.
Kirby, M.
White, D.L.
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Journal article
Citation
Frontiers in Oncology, 2022; 12:851572-1-851572-6
Statement of Responsibility
Susan L. Heatley, Elyse C. Page, Laura N. Eadie, Barbara J. McClure, Jacqueline Rehn, David T. Yeung, Michael Osborn, Tamas Revesz, Maria Kirby, and Deborah L. White
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Abstract
Children with neurofibromatosis have a higher risk of developing juvenile myelomonocytic leukemia and acute myeloid leukemia, but rarely develop B-cell acute lymphoblastic leukemia (B-ALL). Through in-vitro modeling, a novel NF1 p.L2467 frameshift (fs) mutation identified in a relapsed/refractory Ph-like B-ALL patient with neurofibromatosis demonstrated cytokine independence and increased RAS signaling, indicative of leukemic transformation. Furthermore, these cells were sensitive to the MEK inhibitors trametinib and mirdametinib. Bi-allelic NF1 loss of function may be a contributing factor to relapse and with sensitivity to MEK inhibitors, suggests a novel precision medicine target in the setting of neurofibromatosis patients with B-ALL.
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Copyright © 2022 Heatley, Page, Eadie,McClure, Rehn, Yeung, Osborn, Revesz, Kirby and White. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.