Frontiers in Oncology (Apr 2022)
Case Report: Precision Medicine Target Revealed by In Vitro Modeling of Relapsed, Refractory Acute Lymphoblastic Leukemia From a Child With Neurofibromatosis
- 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
Affiliations
- Susan L. Heatley
- Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
- Susan L. Heatley
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- Susan L. Heatley
- Australian & New Zealand Children’s Haematology/Oncology Group, Clayton, VIC, Australia
- Elyse C. Page
- Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
- Elyse C. Page
- Faculty of Science, University of Adelaide, Adelaide, SA, Australia
- Laura N. Eadie
- Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
- Laura N. Eadie
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- Barbara J. McClure
- Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
- Barbara J. McClure
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- Jacqueline Rehn
- Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
- Jacqueline Rehn
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- David T. Yeung
- Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
- David T. Yeung
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- David T. Yeung
- Dept of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia
- David T. Yeung
- Australasian Leukaemia & Lymphoma Group, Richmond, VIC, Australia
- Michael Osborn
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- Michael Osborn
- Australian & New Zealand Children’s Haematology/Oncology Group, Clayton, VIC, Australia
- Michael Osborn
- Australasian Leukaemia & Lymphoma Group, Richmond, VIC, Australia
- Michael Osborn
- Dept of Haematology & Oncology, Women’s & Children’s Hospital, Adelaide, SA, Australia
- Tamas Revesz
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- Tamas Revesz
- Australian & New Zealand Children’s Haematology/Oncology Group, Clayton, VIC, Australia
- Tamas Revesz
- Dept of Haematology & Oncology, Women’s & Children’s Hospital, Adelaide, SA, Australia
- Maria Kirby
- Australian & New Zealand Children’s Haematology/Oncology Group, Clayton, VIC, Australia
- Maria Kirby
- Dept of Haematology & Oncology, Women’s & Children’s Hospital, Adelaide, SA, Australia
- Deborah L. White
- Cancer Program, Precision Medicine Theme, South Australian Health & Medical Research Institute, Adelaide, SA, Australia
- Deborah L. White
- Faculty of Health & Medical Science, University of Adelaide, Adelaide, SA, Australia
- Deborah L. White
- Australian & New Zealand Children’s Haematology/Oncology Group, Clayton, VIC, Australia
- Deborah L. White
- Faculty of Science, University of Adelaide, Adelaide, SA, Australia
- Deborah L. White
- Australasian Leukaemia & Lymphoma Group, Richmond, VIC, Australia
- Deborah L. White
- Australian Genomics Health Alliance, Parkville, VIC, Australia
- DOI
- https://doi.org/10.3389/fonc.2022.851572
- Journal volume & issue
-
Vol. 12
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.
Keywords
