Hematopoietic neoplasia in kit^D814Vflox Mx1-Cre animals. Fifteen of 39 kit^D814Vflox Mx1-Cre animals developed B-cell lineage malignancy in addition to mastocytosis. (A) Histology of a solid lymphoid tumor (hematoxylin and eosin staining, 40×/0.75 NA objective). (B) Tumor cells showed immunoreactivity for the B-lineage marker B220 (40×/0.75 NA objective). (C) Top panel: Flow cytometric analysis of spleen cell suspensions from a control mouse and a kit^D814Vflox Mx1-Cre animal that displayed leukemic disease with large nodular tumors. In addition to the normal splenic B-cell population (R1), a population of CD19⁺ B220 intermediate cells (R2) expressing kit (right panel) appears in the mutant mouse. Bottom panel: The same populations of normal B cells and neoplastic cells were identified in tumor cell suspensions, blood, and bone marrow (neoplastic B220 intermediate cells dominate in tumor and bone marrow). (D) Sequence analysis of reverse-transcribed polymerase chain reaction product obtained from neoplastic B-lineage cells detected only kitD814V, but not wt kit transcript.