Figure 6.
Leukemia in the 3q21q26-EVI1::Gata2+/gfpmice with high platelets has characteristics similar to those of human patients with AML harboring 3q rearrangements. (A) Representative peripheral blood smears (Wright-Giemsa staining) from leukemic 3q21q26-EVI1::Gata2+/gfp mice (High-Mk type leukemia). Note that Blast cells (white arrowheads), myeloid cells (yellow arrowhead), micromegakaryocytes (black arrowheads), and giant platelets (arrow) are observed. (B) Representative flow cytometric profiles of bone marrow cells from leukemic 3q21q26-EVI1::Gata2+/gfp mice (High-Mk type leukemia). CD41– and CD41+CD61+ fractions were further subdivided to assess granulocytic and blast cell characteristics. (C) Representative c-Kit expression profile in each fraction from leukemic 3q21q26-EVI1::Gata2+/gfp mice (High-Mk type leukemia). (D) Wright-Giemsa staining of leukemic cells from 3q21q26-EVI1::Gata2+/gfp bone marrows. (E) Relative mRNA levels of EVI1 and mouse endogenous Gata2 mRNA in each population. B220+Gr1–CD41– (red), B220–Gr1+CD41– (orange), B220–Gr1–CD41– (green), and B220–Gr1–CD41+CD61+ (blue) cells are shown. The abundance of the mRNA was normalized to glyceraldehyde-3-phosphate dehydrogenase. Average values of B220+Gr1–CD41– population were set to 1. Values represent the means ± SD. *P < .05; **P < .01 (1-way ANOVA). (F) Schema for the transplantation analysis; 5 × 104 CD41+B220–Gr1–, CD41–B220+Gr1–, and CD41–B220–Gr1+ cells from leukemic 3q21q26-EVI1::Gata2+/gfp (High-Mk type leukemia, CD45.1/CD45.2 heterozygotes or CD45.1 homozygous) mice were independently transplanted into sublethally irradiated CD45.2 homozygous WT mice. (G) Kaplan-Meier survival curves of WT mice receiving CD41+B220–Gr1–, CD41–B220+Gr1–, and CD41–B220–Gr1+ cells from leukemic 3q21q26-EVI1::Gata2+/gfp mice (High-Mk type leukemia). (H) Representative flow cytometric patterns of the bone marrows of recipient mice receiving CD41–B220+Gr1– cells.