The Bcr/Abl Y177F mutant preferentially induces T-lymphoid leukemia.

(A) Photomicrograph of section of abdominal tumor that developed 105 days after transplantation with p210 Y177F-transduced marrow (mouse 4, Table 1), hematoxylin–eosin stain, magnification 400×. Note the population of cells with large nuclei, prominent nucleoli, and moderate cytoplasm and the frequent mitotic and apoptotic figures (arrowheads). (B) Flow cytometric analysis of tumor cells from A, demonstrating uniform expression of Thy1.2, CD43, and CD24, variable expression of CD8, but lack of expression of the B-lymphoid marker B220 and myeloid marker Mac1. In each panel, expression of the indicated antigen is shown by the gray plot, whereas staining by an isotype control antibody is shown by the transparent plot. (C) Southern blot analysis of T-lymphoid tumor DNA. Left panel: genomic DNA from abdominal tumor (tum) and thymus (thy) from p210 Y177F mouse 4 demonstrates a single proviral integrant when hybridized with a radioactive probe from the retroviral neo gene, whereas thymus DNA from mouse 8 exhibits 2 different proviral clones. Control DNA (C) demonstrates the intensity of 1 proviral copy per diploid genome. Right panel: tumor and thymus DNA from both these mice show loss of the germline band of the T-cell receptor β chain locus (indicated by the GL arrowhead in the control sample) and clonal rearrangements of both alleles when hybridized with a TCRβ probe. Note the thymic lymphoma from mouse 8 shows 4 new bands, corresponding to distinct biallelic rearrangements in each of the 2 clones. Positions of DNA size markers (in kb) are indicated on the left.