Icsbp^−/−Nf1^+/− mice develop different types of leukemias; myeloid leukemias are predominant. Leukemias were classified according to diagnostic criteria established by Kogan et al.³⁰  (A) Flow cytometry staining of leukemias: hematologic organs stained with the myeloid (Gr-1, CD11b) and a B-lymphoid marker (B220) showed differences in maturation and cell composition of the different forms of leukemia in comparison to mice without leukemias. MPD-like leukemias showed highest expression of myeloid and low expression of lymphoid markers in BM and spleen, whereas lymphatic leukemias showed little residual myelopoiesis in BM (n = 10, MPD-like myeloid leukemia; n = 5, myelomonocytic leukemia; n = 1, lymphatic leukemia: n = 5, preleukemic mice). (B) Cytomorphology of leukemias: myelomonocytic leukemias displayed a high percentage of myeloblasts with residual myeloid maturation, whereas lymphatic leukemias showed a high percentage of blast cells with little residual myeloid maturation. Mice without disease manifestation were characterized by high neutrophil granulocyte maturation as typical for Icsbp^−/− mice (g indicates neutrophil granulocyte; l, lymphocyte; and b, blast). Pictures were taken with an Olympus BX41 microscope, equipped with a 40× UPlanFLN 0.75 objective with eyepiece UIS2 WHN 10×, in air. Slides were stained with hematoxylin and eosin. Electronic pictures were taken with a ColorView II version 2.0 camera (SIS, Münster, Germany). Images were acquired with analySIS docu, version 5.0 (SIS) and used without further processing. (C) Histology of tumor infiltrates. Disease-specific massive organ infiltration in spleen, submandibulary lymph nodes with extensive extramedullary hematopoiesis, and liver with mature and blastic (i-iii) in MPD-like leukemia or predominantly myeloblastic cells in myelomonocytic leukemia (iv-ix) was observed. Lymphatic leukemia showed infiltration with lymphocytes without differentiation pattern and large blasts (x-xii). In several instances, eosinophil crystalloid depositions (Charcot-Leyden crystals) were observed (ii). Organs from Icsbp^−/−Nf1^+/− mice without disease manifestation showed little infiltration with granulocytes and blasts (xiii-xv). Organs were stained with hematoxylin and eosin. Original magnification ×400. Pictures were taken with a Leica DMRB microscope, equipped with a 100× NPlan 1.25 objective with eyepiece magnification LPlan 10×, in oil. Slides were stained with May-Gruenwald. Electronic pictures were taken with an Insight camera 4.0 (Visitron Diagnostic Instruments, Sterling Heights, MI). Images were acquired and processed with SpotSoftware 4.1. (Visitron Diagnostic Instruments).