Stat5a and Stat5b both restore myeloproliferation when coexpressed with TEL-PDGFRB in Stat5a-deficient bone marrow cells
| Construct . | Phenotype . | Median survival, d . | P . | n . |
|---|---|---|---|---|
| TPiGFP into Stat5a+/+ | Fatal MPD: 6 | 31 ± 2.6 | — | 15 |
| TPiGFP into Stat5a+/− | Fatal MPD: 2; MPD: 5 | 145 ± 16.0 | < .001 | 19 |
| TPiGFP into Stat5a−/− | Fatal MPD: 1; MPD: 8 | 144 ± 4.1 | < .001 | 17 |
| TPiStat5a add-back into Stat5a+/− | Fatal MPD: 1 | 28 ± 9.0 | .732 | 6 |
| TPiStat5a add-back into Stat5a−/− | Fatal MPD: 6; MPD: 2 | 96 ± 35.5 | < .001 | 12 |
| TPiStat5b add-back into Stat5a−/− | MPD: 2 | 97 ± 7.5 | < .001 | 8 |
| Construct . | Phenotype . | Median survival, d . | P . | n . |
|---|---|---|---|---|
| TPiGFP into Stat5a+/+ | Fatal MPD: 6 | 31 ± 2.6 | — | 15 |
| TPiGFP into Stat5a+/− | Fatal MPD: 2; MPD: 5 | 145 ± 16.0 | < .001 | 19 |
| TPiGFP into Stat5a−/− | Fatal MPD: 1; MPD: 8 | 144 ± 4.1 | < .001 | 17 |
| TPiStat5a add-back into Stat5a+/− | Fatal MPD: 1 | 28 ± 9.0 | .732 | 6 |
| TPiStat5a add-back into Stat5a−/− | Fatal MPD: 6; MPD: 2 | 96 ± 35.5 | < .001 | 12 |
| TPiStat5b add-back into Stat5a−/− | MPD: 2 | 97 ± 7.5 | < .001 | 8 |
Median survival of mice in each cohort is shown with standard error. Disease phenotype at time of death was characterized as either fatal MPD (WBC, > 50 × 109/L [50 000/μL] and spleen weight, > 450 mg) or MPD (WBC, > 15 × 109/L [15 000/μL] and/or spleen weight, > 450 mg) with number of analyzed mice indicated. Statistical significance in survival between TPiGFP → Stat5+/+ and each cohort is shown by P value (determined by Mantel-Cox log rank). Statistical significance in survival between cohorts is determined by log rank (Mantel-Cox) such that the difference in survival of TPiGFP→Stat5a−/− and TPiStat5b→Stat5a−/− has a P value of .01 and the difference in TPiStat5a→Stat5a−/− and TPiStat5b→Stat5a−/− cohort survival has a P value of .79. TPiStat5a → Stat5a+/− mice developed severe MPD (spleen weight, 520 mg [n = 1]; WBC, 66 × 109/L [66 000/μL] [n = 1]). Moderate MPD was detected in TPiStat5a → Stat5a−/− mice (spleen weight median, 800 ± 170 mg; range, 550-970 mg [n = 8]; WBC median, 82 ± 106 × 109/L [82 000 ± 106 000/μL]; range, 40-108 × 109/L [40 000-108 000/μL] [n = 7]) and TPiStat5b → Stat5a−/− mice (spleen weight median, 470 ± 184 mg; range, 340-600 mg [n = 2]; WBC median, 23 ± 10 × 109/L [23 000 ± 10 000/μL]; range, 16-30 × 109/L [16 000-30 000/μL] [n = 2]). TPiGFP indicates TEL-PDGFRB ires eGFP; TPiStat5a, TEL-PDGFRB ires mStat5a; TPiStat5b, TEL-PDGFRB ires Stat5b; MPD, myeloproliferative disease; and WBC, peripheral white blood cell count; and —, not applicable.