Case Report: Precision Medicine Target Revealed by In Vitro Modeling of Relapsed, Refractory Acute Lymphoblastic Leukemia From a Child With Neurofibromatosis
oleh: Susan L. Heatley, Susan L. Heatley, Susan L. Heatley, Elyse C. Page, Elyse C. Page, Laura N. Eadie, Laura N. Eadie, Barbara J. McClure, Barbara J. McClure, Jacqueline Rehn, Jacqueline Rehn, David T. Yeung, David T. Yeung, David T. Yeung, David T. Yeung, Michael Osborn, Michael Osborn, Michael Osborn, Michael Osborn, Tamas Revesz, Tamas Revesz, Tamas Revesz, Maria Kirby, Maria Kirby, Deborah L. White, Deborah L. White, Deborah L. White, Deborah L. White, Deborah L. White, Deborah L. White
| Format: | Article |
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| Diterbitkan: | Frontiers Media S.A. 2022-04-01 |
Deskripsi
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.