Myeloproliferative disease in mice receiving ΔActin BCR-ABL bone marrow is indistinguishable from wild-type P210^BCR-ABL. (A) All lethally irradiated mice receiving transplanted bone marrow expressing either wild-type P210^BCR-ABL (○) or ΔActin BCR-ABL (▵) bone marrow showed evidence of disease by 14 days after transplantation. The latency between wild-type P210^BCR-ABL and ΔActin mice was not significantly different (P = .38), whereas mice given bone marrow expressing the MigRI control vector (□) are healthy within this interval and remain disease free for more than 300 days.¹⁴  (B) Spleens harvested from wild-type P210^BCR-ABL or ΔActin mice were lysed and fractionated on a Western blot to show expression of P210^BCR-ABL or ΔActin at the appropriate size. 32D cells transduced with either P210^BCR-ABL or ΔActin were used as a control. Expression of BCR-ABL could not be detected in spleens of ΔActin mice using an antibody to the extreme C-terminus of BCR-ABL, confirming that the C-terminal actin-binding domain was absent in these mice (data not shown). (C) Sections of peripheral blood (40 ×), bone marrow (20 ×), spleen (4 ×), liver (20 ×), and lung (4 ×) were stained with hematoxylin and eosin or Wright stain (peripheral blood). Mature myeloid cells are present in the peripheral blood, and the normal architecture of each organ is replaced by infiltrative granulocytes. Lungs of the ΔActin mice were less hemorrhagic than of P210^BCR-ABL mice. (D) A representative flow cytometry profile of peripheral blood from wild-type P210^BCR-ABL and ΔActin mice is shown. Peripheral blood, bone marrow, and spleen from wild-type P210^BCR-ABL or ΔActin mice were harvested and stained for the myeloid markers GR-1 and Mac-1. Most cells from each organ of mice from both cohorts stained GR-1⁺/Mac-1⁺, indicating infiltrative granulocytic disease.