Case Report: Precision medicine target revealed by in-vitro modelling of relapsed, refractory ALL from a child with neurofibromatosis

Children with neurofibromatosis have a higher risk of developing juvenile myelomonocytic leukaemia and acute myeloid leukaemia, but rarely develop B-cell acute lymphoblastic leukaemia (B-ALL). Through in-vitro modelling, 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 signalling, indicative of leukaemic 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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001008702	Dataset contains 5 exome BAM files from a child with neurofibromatosis and relapsed refractory acute lymphoblastic leukaemia. The samples are CD19 positive and CD19 negative bone marrow mononuclear cells at both diagnosis and relapse as well as mesenchymal stem cells as the germline control. Libraries were prepared using the SureSelect Clinical Research Exome v2 kit (Agilent Technologies, Santa Clara, CA, USA) and run on the Illumina NextSeq 500 platform.	NextSeq 500	5

Publications	Citations
Case Report: Precision Medicine Target Revealed by <i>In Vitro</i> Modeling of Relapsed, Refractory Acute Lymphoblastic Leukemia From a Child With Neurofibromatosis. Heatley SL, Page EC, Eadie LN, McClure BJ, Rehn J, Yeung DT, Osborn M, Revesz T, Kirby M, White DL. Front Oncol 12: 2022 851572	1