Fig. 4.
Distinct target cells for different leukemias induced by p210 BCR/ABL Y177F and v-abl.
(A) Unique proviral integrants in myeloid cells from mice with T lymphoma and increased neutrophils. Genomic DNA from thymus (thy), abdominal tumor (tum), ascites (asc), spleen (spl), liver (liv), and peripheral blood (pb) of p210 Y177F mouse 7, and tumor, ascites, pleural effusion (eff), peripheral blood, and bone marrow (bm) of mouse 8 (Figure 2, Table 1) were analyzed by Southern blot for provirus integration pattern using a neo probe. In mouse 7 the thymus, tumor, and ascites were composed exclusively of malignant T-lymphoid cells, the liver was a mixture of T-lymphoma and myeloid cells, and the spleen and peripheral blood were exclusively maturing neutrophils (peripheral blood leukocyte count = 356 000/μL). A single provirus is present in the T-lymphoma cells with a distinct single proviral clone in neutrophils. In mouse 8, the tumor was composed exclusively of T-lymphoma cells, the ascites and pleural effusion were mostly lymphoma cells with a small amount of myeloid cells, the peripheral blood was 30% lymphoblasts and 70% neutrophils (peripheral blood leukocyte count = 48 000/μL), and the bone marrow was 50% lymphoblasts and 50% myeloid cells. Again, there is a single provirus in the T-lymphoma cells and a different single proviral clone in the myeloid cells. DNA from a control cell line (con) indicates 1 proviral copy per diploid genome. Positions of DNA size markers (in kb) are indicated on the left. (B) Unique proviral integrants in spleen from mice with v-abl–induced B-lymphoid leukemia and simultaneous macrophage or mast cell disease. Genomic DNA from spleen (spl) and lymph node (LN) from 2 representative mice (animals 1 and 8 in Figure 2, Table 2) with v-abl–induced B-lymphoid leukemia and coexisting macrophage and mast cell tumors (1) or mast cell tumors (8) were analyzed as in A. Lymph nodes from both mice were composed exclusively of malignant lymphoblasts, whereas spleen contained a mixture of lymphoblasts and infiltrating malignant macrophages or mast cells. B lymphoblasts from mouse 1 contained 2 proviral clones, and 4 additional integrants were present in spleen DNA. Similarly, the B-lymphoid disease was biclonal in mouse 8, with 2 additional integrants detected in spleen. DNA from a control cell line (con) indicates 1 proviral copy per diploid genome. Positions of DNA size markers (in kb) are indicated on the left.