SALL4B transgenic mice have an MDS-like/AML phenotype. (A) MDS-like changes in SALL4B transgenic mice. Giemsa staining of peripheral blood from normal, age-matched WT littermates showed normal neutrophils (i), and normal red blood cells and platelets (ii, black arrow). In transgenic mice, neutrophils were hypersegmented (v), and pseudo-Pelger-Huet-like atypical white cells were present (vi-viii), together with increased numbers of immature cells (ix-xi). Nucleate red cells (xii, red arrow), giant platelets (xiii, red arrow), and polychromasia (xiv) were also observed in the transgenic mice. A binucleate dysplastic erythrocyte (xv, red arrow) and a dysplastic megakaryocyte with a hypolobulated nucleus (xvi, red arrow) were found in the cytospin from transgenic mouse bone marrow. An erythroid precursor (iii) and a megakaryocyte (iv) from WT control animals are shown for comparison. (B) AML (AML is defined as blast count more than 20% in peripheral blood and/or bone marrow with multiple organ involvements) observed in SALL4B transgenic mice (mouse 25). Blasts were present in the peripheral blood (i, × 600), bone marrow biopsy specimen (ii, × 100; iii, × 400), bone marrow smear (iv, × 600), liver (v, × 100), lymph node (vi, × 400), and spleen (vii-viii, gross view; ix, × 100; and the inset, × 400). (C) Flow cytometric analysis of leukemia in SALL4B transgenic mice. Leukemia cells from bone marrow, spleen, and lymph nodes were positive for CD45 and myeloid markers such as c-kit, Gr-1, and Mac-1, and negative for B cells (B220), T cells (CD3), and erythrocytes (Ter119). Numbers in quadrants indicate the percentage of total cells. (D) Serial transplantation of SALL4B-induced AML to NOD/SCID mice. Gross picture (i-ii) and histology (iii-vi, × 200) on splenomegaly (i [black arrow], iii), hepatomegaly (i [double black arrows], iv), lymph node enlargement (ii [black arrow], v), and pale kidney (ii [double black arrows], vi) caused by leukemia infiltration in a NOD/SCID mouse 6 weeks after leukemia transplantation.