Figure 2.
The novel oncogenic G3BP1-PDGFRB fusion protein responds to targeted inhibition. (A) Treatment course of the index patient. The G3BP1-PDGFRB fusion transcript was detectable in all heme fusion targeted RNA-sequencing assays, albeit at lower levels, after initiation of imatinib. To normalize for sequencing depth across different assays, the G3BP1-PDGFRB transcript count was normalized to a highly expressed transcript, PICALM. (B) Schematic representation of the constructs used to overexpress fusion transcripts ETV6-PDGFRB, G3BP1-PDGFRB, and truncated PDGFRB (exons 12-23) in Ba/F3 cell lines. (C) GFP expression measured by flow cytometric analysis confirms overexpression of transduced PDGFRB constructs. Dark gray = untransduced. (D) Outgrowth of transduced cells over the indicated time frame, starting from 1% to 5% transduced cell populations. Black = empty vector. (E) Lysate of Ba/F3 cells with G3BP1-PDGFRB, ETV6-PDGFRB, or empty vector (mock) with or without IL-3. (F) Viability of Ba/F3 cells exposed to ranges of tyrosine kinase inhibitors assessed by CellTiter-Glo. Experiments were performed in triplicate. Error bars indicate standard deviation.

The novel oncogenic G3BP1-PDGFRB fusion protein responds to targeted inhibition. (A) Treatment course of the index patient. The G3BP1-PDGFRB fusion transcript was detectable in all heme fusion targeted RNA-sequencing assays, albeit at lower levels, after initiation of imatinib. To normalize for sequencing depth across different assays, the G3BP1-PDGFRB transcript count was normalized to a highly expressed transcript, PICALM. (B) Schematic representation of the constructs used to overexpress fusion transcripts ETV6-PDGFRB, G3BP1-PDGFRB, and truncated PDGFRB (exons 12-23) in Ba/F3 cell lines. (C) GFP expression measured by flow cytometric analysis confirms overexpression of transduced PDGFRB constructs. Dark gray = untransduced. (D) Outgrowth of transduced cells over the indicated time frame, starting from 1% to 5% transduced cell populations. Black = empty vector. (E) Lysate of Ba/F3 cells with G3BP1-PDGFRB, ETV6-PDGFRB, or empty vector (mock) with or without IL-3. (F) Viability of Ba/F3 cells exposed to ranges of tyrosine kinase inhibitors assessed by CellTiter-Glo. Experiments were performed in triplicate. Error bars indicate standard deviation.

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