Figure 6
Figure 6. The JAK2V617F/Rap1/Akt pathway is involved in increased PV RBC adhesion to laminin. All results shown in this figure were obtained with blood samples from the same 6 patients with PV. (A) Effect of JAK2, Rap1, or Akt inhibitors (Z3, GGTI, or Akti, respectively) on RBC adhesion to laminin at 2 dyn/cm2, determined with blood samples obtained from 6 patients with PV. Paired t test, **P < .01 and ***P < .001, compared with untreated RBCs (UT). (B) Quantification of Rap1-GTP in a control “C” and a PV patient blood samples, in the absence (PV UT) or presence (PV Z3) of Z3. The top and bottom panels show the amounts of Rap1-GTP and total Rap1, respectively. The GTP-bound fraction is determined by the Rap1-GTP/Rap1 ratio, with the ratio of the C column being the reference value. (C) Quantification of Rap1-GTP in blood samples from 6 controls “C” and 6 PV patients, in the absence (PV UT) or presence (PV Z3) of Z3, paired t test, ***P < .001 compared with C, ###P < .001 compared with PV UT (n = 6). (D) Quantification of Akt activity in the same control “C” and PV blood samples in the absence (UT) or presence of Z3, GGTI, or Akti. Horizontal bars indicate medians; Mann-Whitney test, **P < .01, compared with C, ##P < .01 compared with PV UT. (E) Quantification of Lu phosphorylation in a blood sample of a PV patient, in the absence (UT) or presence of Z3, GGTI, or Akti. The phosphorylated fraction is determined by the P/WB ratio, with the ratio of the UT column being the reference value. (F) Quantification of Lu/BCAM phosphorylation in blood samples from the 6 PV patients, in the absence (UT) or presence of the same inhibitors, paired t test, ***P < .001 compared with UT.

The JAK2V617F/Rap1/Akt pathway is involved in increased PV RBC adhesion to laminin. All results shown in this figure were obtained with blood samples from the same 6 patients with PV. (A) Effect of JAK2, Rap1, or Akt inhibitors (Z3, GGTI, or Akti, respectively) on RBC adhesion to laminin at 2 dyn/cm2, determined with blood samples obtained from 6 patients with PV. Paired t test, **P < .01 and ***P < .001, compared with untreated RBCs (UT). (B) Quantification of Rap1-GTP in a control “C” and a PV patient blood samples, in the absence (PV UT) or presence (PV Z3) of Z3. The top and bottom panels show the amounts of Rap1-GTP and total Rap1, respectively. The GTP-bound fraction is determined by the Rap1-GTP/Rap1 ratio, with the ratio of the C column being the reference value. (C) Quantification of Rap1-GTP in blood samples from 6 controls “C” and 6 PV patients, in the absence (PV UT) or presence (PV Z3) of Z3, paired t test, ***P < .001 compared with C, ###P < .001 compared with PV UT (n = 6). (D) Quantification of Akt activity in the same control “C” and PV blood samples in the absence (UT) or presence of Z3, GGTI, or Akti. Horizontal bars indicate medians; Mann-Whitney test, **P < .01, compared with C, ##P < .01 compared with PV UT. (E) Quantification of Lu phosphorylation in a blood sample of a PV patient, in the absence (UT) or presence of Z3, GGTI, or Akti. The phosphorylated fraction is determined by the P/WB ratio, with the ratio of the UT column being the reference value. (F) Quantification of Lu/BCAM phosphorylation in blood samples from the 6 PV patients, in the absence (UT) or presence of the same inhibitors, paired t test, ***P < .001 compared with UT.

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