AUTHOR=Heatley Susan L. , Page Elyse C. , Eadie Laura N. , McClure Barbara J. , Rehn Jacqueline , Yeung David T. , Osborn Michael , Revesz Tamas , Kirby Maria , White Deborah L. 

TITLE=Case Report: Precision Medicine Target Revealed by In Vitro Modeling of Relapsed, Refractory Acute Lymphoblastic Leukemia From a Child With Neurofibromatosis

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.851572

DOI=10.3389/fonc.2022.851572

ISSN=2234-943X

ABSTRACT=<p>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 <italic>in-vitro</italic> modeling, a novel <italic>NF1</italic> 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 <italic>NF1</italic> 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.</p>