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Blood, Vol. 109, Issue 5, 2147-2155, March 1, 2007

Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation
Blood Wang et al.
109: 2147
Supplemental materials for: Wang et al, Vol 109, Issue 5, 2147-2155
Files in this Data Supplement:
- Table S1. Patient characteristics (PDF, 18.3 KB) -
AP indicates accelerated phase; BC, blast crisis; HU, hydroxyurea; PBMCs, peripheral blood mononuclear cells; and no., CD34 cells were enriched by magnetic bead selection.
- Table S2. Patient characteristics of IM-resistant patients for GM-CSF PCR (PDF, 9.5 KB) -
AP/BC indicates accelerated phase/blast crisis; DAS, dasatinib; polym., polymorphism; n.a., not available; f, female; and m, male.
- Table S3. Patient characteristics of IM-resistant patients for GM-CSF ELISA (PDF, 9.66 KB)
- Figure S1. BCR/ABL–independent, JAK-2–dependent STAT-5 activation by GM-CSF in IM-naive CML progenitors (PDF, 69.6 KB) -
CD34+-enriched primary CML progenitors of patient no. 6 (de novo CML) were treated for 48 hours with NI (10 µM) and the JAK-2 inhibitor AG490 (100 µM) with or without GM-CSF (10 ng/mL), and analyzed by FACS for the regulation of ic-p-STAT-5 (top 2 histograms) and ic-p-CrkL (bottom histograms) according to the following gating strategy: CD34high/CD116low (gate R1) or CD116high (gate R2). The gray curves in each histogram represent baseline expression levels.
- Figure S2. GM-CSF overcomes NI-mediated inhibition of colony formation of IM-naive CML progenitors (PDF, 16.4 KB) -
CD34+ enriched progenitors from a patient with first-diagnosis CML (patient no. 7) were cultured in vitro in the presence of 10 µM NI in IMDM containing 20% FCS and 5GF with or without GM-CSF, as indicated. After 72 hours, cells were seeded into soft agar, and 10 to14 days later, emerging colonies (CFCs) were counted. Bars show CFC counts (colonies) after the respective treatment. *P < .05; **P < .01 (1-way ANOVA, Dunnett adjustment for multiple testing).
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