Figure 3
Figure 3. Stat5a gene dosage mediates the latency of TEL-PDGFRB–induced myeloproliferation. (A) Kaplan-Meier plot shows survival of recipient mice when TEL-PDGFRB is expressed in bone marrow cells harboring homozygous or heterozygous inactivation of Stat5a. TPiGFP→Stat5a+/+ mice (circles) developed severe MPD (spleen weight median, 790 ± 90 mg; range, 620-910 mg; n = 6). TPiGFP→Stat5a+/− mice (▵) developed moderate or severe MPD (spleen weight median, 770 ± 300 mg; range, 350-1120 mg; n = 7). TPiGFP→Stat5a−/− mice (squares) developed moderate MPD with splenomegaly (spleen weight, 710 ± 550 mg; range, 350-2070 mg; n = 8) and leukocytosis. Black shapes indicate death due to severe (fatal) MPD marked by leukocytosis and splenomegaly (WBC, > 50 × 109/L [50 000/μL] and spleen weight, > 450 mg) at time of death due to disease. Shaded shapes represent moderate MPD (WBC, > 15 × 109/L [15 000/μL] and/or spleen weight, > 450 mg) at time of death due to disease. Open shapes indicate animal found dead. (B) Median peripheral blood cell count at time of death due to disease. Error bars represent standard deviation. TEL-PDGFRB induced severe leukocytosis in TPiGFP→Stat5a+/+ mice (359 ± 225 × 109/L [359 000 ± 225 000/μL]; range, 60-737 × 109/L [60 000-737 000/μL]; n = 6) and moderate leukocytosis in TPiGFP→Stat5a+/− mice (28 ± 15 × 109/L [28 000 ± 15 000/μL]; range, 12-131 × 109/L [12 000-131 000/μL]; n = 7) as well as TPiGFP→Stat5a−/− mice (29 ± 27 × 109/L [29 000 ± 27 000/μL];range, 10-94 × 109/L [10 000-94 000/μL]; n = 8). (C) Three mice from each cohort were analyzed 28 days after transplantation. Median of peripheral blood counts is shown. Error bars represent standard deviation. Peripheral blood counts of GFP→Stat5a−/− control mice are also shown. (TPiGFP indicates TEL-PDGFRB ires eGFP; MPD, myeloproliferative disease; and WBC, peripheral white blood cell count.)

Stat5a gene dosage mediates the latency of TEL-PDGFRB–induced myeloproliferation. (A) Kaplan-Meier plot shows survival of recipient mice when TEL-PDGFRB is expressed in bone marrow cells harboring homozygous or heterozygous inactivation of Stat5a. TPiGFP→Stat5a+/+ mice (circles) developed severe MPD (spleen weight median, 790 ± 90 mg; range, 620-910 mg; n = 6). TPiGFP→Stat5a+/− mice (▵) developed moderate or severe MPD (spleen weight median, 770 ± 300 mg; range, 350-1120 mg; n = 7). TPiGFP→Stat5a−/− mice (squares) developed moderate MPD with splenomegaly (spleen weight, 710 ± 550 mg; range, 350-2070 mg; n = 8) and leukocytosis. Black shapes indicate death due to severe (fatal) MPD marked by leukocytosis and splenomegaly (WBC, > 50 × 109/L [50 000/μL] and spleen weight, > 450 mg) at time of death due to disease. Shaded shapes represent moderate MPD (WBC, > 15 × 109/L [15 000/μL] and/or spleen weight, > 450 mg) at time of death due to disease. Open shapes indicate animal found dead. (B) Median peripheral blood cell count at time of death due to disease. Error bars represent standard deviation. TEL-PDGFRB induced severe leukocytosis in TPiGFP→Stat5a+/+ mice (359 ± 225 × 109/L [359 000 ± 225 000/μL]; range, 60-737 × 109/L [60 000-737 000/μL]; n = 6) and moderate leukocytosis in TPiGFP→Stat5a+/− mice (28 ± 15 × 109/L [28 000 ± 15 000/μL]; range, 12-131 × 109/L [12 000-131 000/μL]; n = 7) as well as TPiGFP→Stat5a−/− mice (29 ± 27 × 109/L [29 000 ± 27 000/μL];range, 10-94 × 109/L [10 000-94 000/μL]; n = 8). (C) Three mice from each cohort were analyzed 28 days after transplantation. Median of peripheral blood counts is shown. Error bars represent standard deviation. Peripheral blood counts of GFP→Stat5a−/− control mice are also shown. (TPiGFP indicates TEL-PDGFRB ires eGFP; MPD, myeloproliferative disease; and WBC, peripheral white blood cell count.)

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