Figure 4.
Absence of Hoxa7 or Hoxa9 influences the latency, penetrance, and phenotype of MLL-GAS7 AML. (A) Survival curves are shown for cohorts (n = 10) of mice that received transplanted MLL-GAS7-transduced c-Kit+ bone marrow cells derived from wild-type (blue), Hoxa7+/-Hoxa9+/- (green), Hoxa7-/- (pink), or Hoxa9-/- (yellow) mice, or nontransduced wild-type bone marrow cells (black). (B) Typical phenotypic analysis of leukemic blasts from mice that underwent transplantation with transduced wild-type (n = 6), Hoxa7+/-Hoxa9+/- (n = 4), Hoxa7-/- (n = 4), and Hoxa9-/- (n = 4) progenitors. Blue profiles represent FACS staining obtained with antibodies specific for the indicated cell surface antigens. Red profiles represent unstained controls or staining obtained with isotype control antibodies. (C) Histologic analysis of tissues from a mouse that developed T-ALL after transplantation with MLL-GAS7-transduced Hoxa9-/- cells. Original magnification × 1200. (D) TCR gene rearrangement studies of tissues from mice with T-ALL. Thymocytes from normal and E2A-PBX1 transgenic mice were used as negative and positive controls, respectively. Numbers above the positive control lanes refer to sample numbers of the E2A-PBX1 transgenic mice.36 Short and long exposures are shown in upper and lower panels, respectively. gl indicates germline configuration of the TCRβ gene.