Myelodysplastic syndrome

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

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References

  1. 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.

  2. 2.

    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.

  3. 3.

    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.

  4. 4.

    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.

  5. 5.

    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.

  6. 6.

    Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, et al. Integrated molecular profiling of juvenile myelomonocytic leukemia. Blood. 2018;131:1576–86.

  7. 7.

    Baldwin BR, Li L, Tse KF, Small S, Collector M, Whartenby KA, et al. Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease. Leukemia. 2007;21:764–71.

  8. 8.

    Falchi L, Mehrotra M, Newberry KJ, Lyle LM, Lu G, Patel KP, et al. ETV6-FLT3 fusion gene-positive, eosinophilia-associated myeloproliferative neoplasm successfully treated with sorafenib and allogeneic stem cell transplant. Leukemia. 2014;28:2090–2.

  9. 9.

    Stirewalt DL, Kopecky KJ, Meshinchi S, Engel JH, Pogosova-Agadjanyan EL, Linsley J, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood. 2006;107:3724–6.

  10. 10.

    Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752–9.

  11. 11.

    Bown N, Y SM, Evans J, Kernahan J, Reid MM. Chronic myelomonocytic leukemia with t(13;14) in a child. Cancer Genet Cytogenet. 1992;60:190–2. 1992

  12. 12.

    Buijs A, Bruin M. Fusion of FIP1L1 and RARA as a result of a novel t(4;17)(q12; q21) in a case of juvenile myelomonocytic leukemia. Leukemia. 2007;21:1104–8.

  13. 13.

    Morerio CA M, Rosanda C, Rapella A, Dufour C, Locatelli F, Maserati E, et al. HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33; p11.2). Cancer Res. 2014;64:2649–51.

  14. 14.

    Byrgazov K, Kastner R, Dworzak M, Hoermann G, Haas OA, Ulreich R, et al. A novel fusion gene NDEL1-Pdgfrb in a patient with JMML with a new variant of TKI-resistant mutation in the kinase domain of PDGFR beta. Blood. 2014;124:613.

  15. 15.

    Mizoguchi Y, Fujita N, Taki T, Hayashi Y, Hamamoto K. Juvenile myelomonocytic leukemia with t(7;11)(p15; p15) and NUP98-HOXA11 fusion. Am J Hematol. 2009;84:295–7.

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Acknowledgements

We thank the family for their willingness to share their story. This work was supported by the National Institutes of Health, National Cancer Institute grant 1U54CA196519 (M.L.L., E.S.); National Institutes of Health, National Heart, Lung, and Blood Institute grant K08HL135434 (E.S.); Alex’s Lemonade Stand, Center of Excellence (M.L.L., E.S.) and the Frank A. Campini Foundation (M.L.L. and E.S.). C.S. is the Damon Runyon-Richard Lumsden Foundation Clinical Investigator supported (in part) by the Damon Runyon Cancer Research Foundation (CI-99-18).

Author information

A.K.C. and J.A.M. performed the ddPCR and Ba/F3 experiments and analyzed the data; A.G.L. and J.V.Z. analyzed the data; A.K.K., B.S.B., E.A.S., C.C.S., C.C.D., T.T., A.H. all advised on design of the experiments; A.K.C. and E.S. wrote the manuscript; J.A.M., A.G.L., J.V.Z., A.K.K., C.G., B.S.B, E.A.S., C.C.S., C.C.D., M.L.L., T.T., A.H. edited the manuscript; E.S. supervised the experiments; and all authors reviewed the literature, contributed to specific sections, and reviewed the final version of the manuscript.

Correspondence to Elliot Stieglitz.

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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.

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