Figure 5
Figure 5. TEL-PDGFRB–mediated myeloproliferative disease does not require Src family members Lyn, Hck, and Fgr.(A) Retroviral constructs encode TEL-PDGFRB followed by an internal ribosomal entry site to allow expression of a second cDNA, either GFP or c-Src. (B) Kaplan-Meier plot of recipient mouse survival when TEL-PDGFRB is coexpressed with either GFP (□) or c-Src (○) in Hck-, Lyn-, and Fgr-deficient cells. The 4 TPiGFP→Lyn−/−Hck−/−Fgr−/− mice had varying degrees of disease severity (spleen weight, 445 ± 273 mg; range, 270-590 mg; median WBC, 38 ± 66 × 109/L [38 000 ± 66 000/μL]; range, 14-156 × 109/L [14 000-156 000/μL]). MPD was detected in 3 of 3 TPiSrc→ Lyn−/−Hck−/−Fgr−/− mice analyzed for disease severity at time of death (spleen weight median, 590 ± 190 mg; range, 480-850 mg; median WBC, 86 ±839 × 109/L [86 000 ± 839 000/μL]; range, 14-1502 × 109/L [14 000-1 502 000 000/μL]). Black shapes indicate death due to severe 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. (ires indicates internal ribosomal entry site; GFP, green fluorescent protein; LTR, long terminal repeat; PNT, pointed domain; TK, tyrosine kinase; MPD, myeloproliferative disease; and WBC, peripheral white blood cell count.)

TEL-PDGFRB–mediated myeloproliferative disease does not require Src family members Lyn, Hck, and Fgr.(A) Retroviral constructs encode TEL-PDGFRB followed by an internal ribosomal entry site to allow expression of a second cDNA, either GFP or c-Src. (B) Kaplan-Meier plot of recipient mouse survival when TEL-PDGFRB is coexpressed with either GFP (□) or c-Src (○) in Hck-, Lyn-, and Fgr-deficient cells. The 4 TPiGFPLyn−/−Hck−/−Fgr−/− mice had varying degrees of disease severity (spleen weight, 445 ± 273 mg; range, 270-590 mg; median WBC, 38 ± 66 × 109/L [38 000 ± 66 000/μL]; range, 14-156 × 109/L [14 000-156 000/μL]). MPD was detected in 3 of 3 TPiSrcLyn−/−Hck−/−Fgr−/− mice analyzed for disease severity at time of death (spleen weight median, 590 ± 190 mg; range, 480-850 mg; median WBC, 86 ±839 × 109/L [86 000 ± 839 000/μL]; range, 14-1502 × 109/L [14 000-1 502 000 000/μL]). Black shapes indicate death due to severe 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. (ires indicates internal ribosomal entry site; GFP, green fluorescent protein; LTR, long terminal repeat; PNT, pointed domain; TK, tyrosine kinase; MPD, myeloproliferative disease; and WBC, peripheral white blood cell count.)

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