Figure 5
Figure 5. Loss of β-catenin binding limits TCF/LEF signaling and self-renewal of myeloid progenitors and sensitizes the cells to apoptosis. Bone marrow cells isolated from diseased mice at death were used for immunophenotypic and cell cycle analysis of progenitor populations. (A) Representative fluorescence-activated cell sorter staining profiles of progenitor populations. (B) Percentages of each progenitor populations (GMP, CMP, and MEP) relative to total GFP+ cells. Values were derived from at least 4 mice per group and are represented as averages. Data show significant decreases of CMP in BCR/ABL(ΔUBD) mice relative to BCR/ABL mice (P < .01), whereas a significant increase in MEPs was found in BCR/ABL (ΔUBD) mice (P < .05). (C) Cell cycle analysis of CMPs, GMPs, and MEPs in p210 BCR/ABL mice and p210 BCR/ABL(ΔUBD) mice. Values were derived from at least 4 mice per group and are represented as averages. A significant increase of sub G1 cells (P < .001) and decrease of S phase cells (P < .001) were found in the CMPs of BCR/ABL (ΔUBD) mice relative to BCR/ABL mice. A significant increase of sub G1 cells (P < .001) and decrease of S phase cells (P < .01) were found in the GMPs of BCR/ABL (ΔUBD) mice relative to BCR/ABL mice. A significant increase in S phase cells (P < .05) was found in the MEPs of BCR/ABL (ΔUBD) mice relative to BCR/ABL mice. (D) Analysis of β-catenin expression in CMPs and MEPs isolated from p210 BCR/ABL and p210 BCR/ABL(ΔUBD) mice. Data are representative of 3 mice evaluated at death. (E) Comparison of TCF/LEF reporter activity in CMPs and MEPs isolated from diseased mice. Progenitors were isolated at death, cultured, and infected with lentiviral particles containing a TCF/LEF reporter along with Renilla control. Seventy-two hours after transfection, cells were analyzed for luciferase and Renilla activity. Luciferase levels were normalized to the Renilla control, and then p210 BCR/ABL was expressed as fold activation relative to p210 BCR/ABL(ΔUBD). Data shown represent the average of 3 mice at death. **P < .01; ***P < .001. FSC: foward scatter; SSC: side scatter.

Loss of β-catenin binding limits TCF/LEF signaling and self-renewal of myeloid progenitors and sensitizes the cells to apoptosis. Bone marrow cells isolated from diseased mice at death were used for immunophenotypic and cell cycle analysis of progenitor populations. (A) Representative fluorescence-activated cell sorter staining profiles of progenitor populations. (B) Percentages of each progenitor populations (GMP, CMP, and MEP) relative to total GFP+ cells. Values were derived from at least 4 mice per group and are represented as averages. Data show significant decreases of CMP in BCR/ABL(ΔUBD) mice relative to BCR/ABL mice (P < .01), whereas a significant increase in MEPs was found in BCR/ABL (ΔUBD) mice (P < .05). (C) Cell cycle analysis of CMPs, GMPs, and MEPs in p210 BCR/ABL mice and p210 BCR/ABL(ΔUBD) mice. Values were derived from at least 4 mice per group and are represented as averages. A significant increase of sub G1 cells (P < .001) and decrease of S phase cells (P < .001) were found in the CMPs of BCR/ABL (ΔUBD) mice relative to BCR/ABL mice. A significant increase of sub G1 cells (P < .001) and decrease of S phase cells (P < .01) were found in the GMPs of BCR/ABL (ΔUBD) mice relative to BCR/ABL mice. A significant increase in S phase cells (P < .05) was found in the MEPs of BCR/ABL (ΔUBD) mice relative to BCR/ABL mice. (D) Analysis of β-catenin expression in CMPs and MEPs isolated from p210 BCR/ABL and p210 BCR/ABL(ΔUBD) mice. Data are representative of 3 mice evaluated at death. (E) Comparison of TCF/LEF reporter activity in CMPs and MEPs isolated from diseased mice. Progenitors were isolated at death, cultured, and infected with lentiviral particles containing a TCF/LEF reporter along with Renilla control. Seventy-two hours after transfection, cells were analyzed for luciferase and Renilla activity. Luciferase levels were normalized to the Renilla control, and then p210 BCR/ABL was expressed as fold activation relative to p210 BCR/ABL(ΔUBD). Data shown represent the average of 3 mice at death. **P < .01; ***P < .001. FSC: foward scatter; SSC: side scatter.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal