Figure 6.

Loss of 1 copy of Abi-1 accelerates disease development in the bone marrow transplantation model of MPL^W515L-mediated myeloproliferative neoplasm. (A) Schematic representation of Abi-1^HET/MPL^W515L model. Bone marrow was obtained from 14-week-old sex-matched Abi-1^WT (n = 3) or Abi-1^HET (n = 3) animals and transduced with retrovirus encoding Abi-1^WT or W515L mutated GFP-tagged MPL. Infected bone marrows representing 4 experimental groups Abi-1^WT/MPL^WT, Abi-1^HET/MPL^WT, Abi-1^WT/MPL^W515L, or Abi-1^HET/MPL^W515L were next transplanted to C57BL/6J females (n = 6 per experimental group). Analyses were conducted 60 days posttransplant. (B). Representative gross pathology images of femurs, spleens, and livers of the animals from each experimental group are shown. (C) Average spleen and liver sizes of Abi-1^WT/MPL^WT, Abi-1^HET/MPL^WT, Abi-1^WT/MPL^W515L, or Abi-1^HET/MPL^W515L mice. Relative organ weight was calculated as an absolute organ weight (g)/body weight on sacrifice day (g) ×100. Organs from 6 animals per group were evaluated. (D) Average white blood cell count and hematocrit and platelet count of Abi-1^WT/MPL^WT, Abi-1^HET/MPL^WT, Abi-1^WT/MPL^W515L, or Abi-1^HET/MPL^W515L mice. Peripheral blood from 6 animals per group was analyzed. (E) Average frequencies of Mac1⁺/Gr-1⁺, CD41⁺, CD42⁺, CD71⁺/Ter119⁺ or CD71⁺/Ter119⁻ as well as B220⁺ and CD3⁺ cells in the bone marrow or peripheral blood obtained from Abi-1^WT/MPL^WT, Abi-1^HET/MPL^WT, Abi-1^WT/MPL^W515L, or Abi-1^HET/MPL^W515L mice. Samples from 6 animals per group were analyzed. (F) Gomori reticulin staining of the bone marrow from femurs and spleen sections of Abi-1^WT/MPL^W515L or Abi-1^HET/MPL^W515L animals (black stain). Bars correspond to 100 μm. Images were obtained using Zeiss Axiophot microscope with Zeiss Pan-Apochromat 20×/1.0 lens. *P < .05