Figure 4.

Double JAK/TET mutant cells have a clonal advantage and result in a sustained myeloproliferative phenotype in transplantation. Bone marrow transplantations were performed, and peripheral blood was analyzed for donor cell chimerism and blood parameters. Only recipients of double-mutant bone marrow have persistently high hematocrit (A) (P < .01 at 16 weeks) and hemoglobin (B) (P < .01 at 16 weeks). Donor cell chimerism at 16 weeks in primary (C) and secondary (D) transplantations is displayed. Whereas JAK2V617F cells (red bars) are less competitive relative to WT cells (blue bars; P < .01), those with a single TET mutation (green bars) or double mutants (JAK HOM TET HOM, orange bars) were similar to WT cells, indicating no deficiency in self-renewal. (E-F) Mean proportion of E-SLAM HSCs in donor cells in bone marrow, 24 weeks posttransplantation, from primary (E) and secondary (F) recipients. In double-mutant recipients, E-SLAM numbers were not different compared with WT, whereas JAK2 single-mutant recipients have lost both phenotypic and functional HSCs.