Abstract
Rearrangements of chromosome band 9p24 are known to be associated with JAK2 fusion genes, e.g., t(8;9)(p22;p24) with a PCM1-JAK2 and t(9;22)(p24;q11) with a BCR-JAK2 fusion gene, respectively. In association with myeloid neoplasms, the clinical course is aggressive, and in absence of effective conventional treatment options, long-term remission is usually only observed after allogeneic stem cell transplantation (ASCT). With the discovery of inhibitors of the JAK2 tyrosine kinase and based on encouraging in vitro and in vivo data, we treated two male patients with myeloid neoplasms and a PCM1-JAK2 or a BCR-JAK2 fusion gene, respectively, with the JAK1/JAK2 inhibitor ruxolitinib. After 12 months of treatment, both patients achieved a complete clinical, hematologic, and cytogenetic response. Non-hematologic toxicity was only grade 1 while no hematologic toxicity was observed. However, remission in both patients was only short-term, with relapse occurring after 18 and 24 months, respectively, making ASCT indispensable in both cases. This data highlight (1) the ongoing importance of cytogenetic analysis for the diagnostic work-up of myeloid neoplasms as it may guide targeted therapy and (2) remission under ruxolitinib may only be short-termed in JAK2 fusion genes but it may be an important bridging therapy prior to ASCT.
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Acknowledgments
This study was supported by the José Carreras Leukämie-Stiftung e.V. (grant no: R09/29f and H11/03). The authors acknowledge the use of the IRIDIS High Performance Computing Facility, and associated support services at the University of Southampton, in the completion of this work. We are grateful to Barbara Bain for helpful comments on the manuscript.
Conflict of interest
WKH, NCPC, HPH, and AR received honoraria from Novartis Pharma. CH has equity ownership of MLL Munich Leukemia Laboratory GmbH. Ruxolitinib was supplied by Novartis Pharma through an individual supply program. The remaining authors declare no competing financial interests.
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Informed consent was obtained from all patients for being included in this study.
Authors’ contributions
JS, GM, MJ, WKH, and AR provided patient material and information. CH and AF performed cytogenetic analyses. MK, AC, WT, JoS, KW, NN, and NCP performed the laboratory work for the study. HPH reviewed bone marrow biopsies. JS, NCPC, and AR prepared the study design and wrote the manuscript. All authors approved the final version of the manuscript.
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Juliana Schwaab and Marcin Knut contributed equally.
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Schwaab, J., Knut, M., Haferlach, C. et al. Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes. Ann Hematol 94, 233–238 (2015). https://doi.org/10.1007/s00277-014-2221-y
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DOI: https://doi.org/10.1007/s00277-014-2221-y