Myeloproliferative phenotype in mice that received transplants of bone marrow transduced with constructs encoding TEL-PDGFβR variants. (A) Kaplan-Meier survival plot of mice that received transplants of bone marrow cells transduced with distinct TEL-PDGFβR constructs. Mice that received transplants of wild-type TEL-PDGFβR (n = 7), W566A (n = 12), and double mutant W566A/W593A (n = 11) died with a rapidly developed fatal myeloproliferative syndrome. Only 8 of 11 W593A mice that received transplants developed myeloproliferative disease with much longer latency (median survival = 102 days). (B) Spleen cells from representative mice transduced with each of the constructs were stained with allophycocyanin (APC)-conjugated anti-Gr-1 and phycoerythrin (PE)-conjugated anti-Mac-1 and analyzed by flow cytometry. The immunophenotype of cells from spleen tissues of TEL-PDGFβR variants illustrates a high percentage of mature myeloid cells (identified as Gr-1 and Mac-1 double-positive cells) in spleen. The percentage of Gr-1+ Mac-1+ granulocytes in the top right quadrant of the dot plots is indicated. (C) Sections of spleen from the same 4 mice as in panel B were stained with hematoxylin and eosin and shown at an original magnification of × 400. Spleen tissues of TEL-PDGFβR variants demonstrate marked expansion of maturing myeloid elements, many with folded or ringlike nuclei, and small numbers (< 5%) of blast forms compatible with a myeloproliferative disease (nonreactive).