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Case Reports
. 2020 Feb;34(2):662-666.
doi: 10.1038/s41375-019-0549-y. Epub 2019 Sep 12.

Fusion driven JMML: a novel CCDC88C-FLT3 fusion responsive to sorafenib identified by RNA sequencing

Alexander K Chao  1 , Julia A Meyer  1 , Alex G Lee  1 , Anna Hecht  1 , Theodore Tarver  2 , Jessica Van Ziffle  3 , Ashley K Koegel  1 , Carla Golden  4 , Benjamin S Braun  1   5 , E Alejandro Sweet-Cordero  1   5 , Catherine C Smith  2   5 , Christopher C Dvorak  1   5 , Mignon L Loh  1   5 , Elliot Stieglitz  6   7
Affiliations
Case Reports

Fusion driven JMML: a novel CCDC88C-FLT3 fusion responsive to sorafenib identified by RNA sequencing

Alexander K Chao et al. Leukemia. 2020 Feb.
No abstract available

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Conflict of interest statement

Conflict of interest C.S. received research funding from FujiFilm and Astellas Pharma. A.K.C. received an honoraria from Bio-Rad for speaking at a symposium. No other authors declare conflicts of interest.

Figures

Fig. 1
Fig. 1
Clinical course related to CCDC88C–FLT3 fusion. a Colony forming assay of patient PBMCs with increasing concentrations of GM-CSF (mean ± SEM is displayed, n = 4, N = 1). b Schematic timeline of JMML patient course (5-azacitidine is abbreviated as Aza). c Schematic illustration of CCDC88C–FLT3 fusion: the top panel illustrates exon structure indicated by blue (CCDC88C) or green (FLT3) vertical lines. The middle panel shows a Sanger sequence trace from patient cDNA aligned with an annotated sequence of the fusion junction. The lower panel shows an illustration of protein domains from both partners retained in the fusion
Fig. 2
Fig. 2
FLT3 fusion causes cytokine-independent growth and is sensitive to FLT3 inhibition. a Growth rates of Ba/F3 cells transduced with CCDC88C–FLT3, FLT3 ITD, or mock vector after mouse interleukin-3 (mIL3) withdrawal (mean ± SEM is displayed, n = 3, representative of N = 3 independent experiments). b Drug sensitivity of Ba/F3 cells to a 48 h sorafenib exposure. EC50 ± SEM values are reported as the drug concentration that achieves a 50% decrease in luminescence by Cell Titer Glo assay (mean ± SEM is displayed, n = 3, representative of N = 3 independent experiments). c FLT3 fusion transcript levels in patient peripheral blood over time as assayed by RT-ddPCR (mean ± SEM is displayed, n = 3, N = 1)
See this image and copyright information in PMC

References

    1. Stieglitz E, Ward AF, Gerbing RB, Alonzo TA, Arceci RJ, Liu YL, et al. Phase II/III trial of a pre-transplant farnesyl transferase inhibitor in juvenile myelomonocytic leukemia: a report from the Children’s Oncology Group. Pediatr blood cancer. 2015;62: 629–36. - PMC - PubMed
    1. Dvorak CC, Satwani P, Stieglitz E, Cairo MS, Dang H, Pei Q, et al. Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: sa Children’s Oncology Group study. Pediatr blood cancer. 2018;65:e27034. - PMC - PubMed
    1. Stieglitz E, Taylor-Weiner AN, Chang TY, Gelston LC, Wang YD, Mazor T, et al. The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet. 2015;47:1326–33. - PMC - PubMed
    1. Stieglitz E, Troup CB, Gelston LC, Haliburton J, Chow ED, Yu KB, et al. Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia. Blood. 2015;125: 516–24. - PMC - PubMed
    1. Locatelli F, Nollke P, Zecca M, Korthof E, Lanino E, Peters C, et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial. Blood. 2005;105:410–9. - PubMed