- Andrew Chase1,*,
- Catherine Bryant1,
- Joannah Score1,
- Claudia Haferlach2,
- Vera Grossmann2,
- Juliana Schwaab3,
- Wolf-Karsten Hofmann3,
- Andreas Reiter3 and
- Nicholas C.P. Cross1
- 1 University of Southampton, UK;
- 2 MLL Munich Leukemia Laboratory, Germany;
- 3 Universitatsmedizin Mannheim, Germany
- ↵* Corresponding author; email:
JAK2 fusion genes are rare but recurrent abnormalities associated with diverse, clinically heterogeneous hematological malignancies. Here we assess the JAK1/2 inhibitor ruxolitinib as therapy for patients with JAK2-rearrangement associated myeloproliferative neoplasms (MPN). Ruxolitinib-treated Ba/F3 cells transformed to IL3 independence by ETV6-JAK2 showed reduced proliferation and survival (IC50 = 370 nM) compared with KG1A or Ba/F3 cells transformed by BCR-ABL1, SPBN1-FLT3 and ZMYM2-FGFR1 (IC50 > 10 microM for all). Inhibition was associated with reduced phosphorylation of ETV6-JAK2, ERK, STAT5 and AKT. Primary cell growth from two patients with JAK2 rearrangement and one patient with JAK2 amplification was assessed in methylcellulose assays. Reduced colony growth was seen for all patients in ruxolitinib-treated cultures compared with healthy controls (n=7). Fluorescence in-situ hybridization showed reduced growth of JAK2-rearrangement positive colonies compared to JAK2-rearrangement negative colonies. Our data therefore provides evidence that ruxolitinib is a promising therapy for treatment of patients with JAK2 fusion genes.
- Received April 12, 2012.
- Accepted August 1, 2012.
- Copyright © 2012, Ferrata Storti Foundation