Figure 2
Mutant IDH1 induces a myeloproliferative-like disease in immortalized bone marrow cells. (A) Association of IDH1 mutations with expression levels of HOXA9 in adult AML patients up to 60 years of age (n = 457). Normalized expression levels of HOXA9 are shown for patients with wild-type IDH1 (gray bars) and mutant IDH1 (red bars), which were determined on an Affymetrix microarray with 2 different probes.31 (B) Protein expression of HoxA9-immortalized cells transduced with a CTL vector or with FLAG-tagged wild-type IDH1 or mutant IDH1 using an anti-FLAG antibody. β-actin was probed on the same blot as a loading control. (C) Ratio of R-2HG to S-2HG in cultured HoxA9 cells transduced with CTL, IDH1wt, or IDH1mut (mean ± SEM of 4 independently transduced cell lines). (D) Engraftment of transduced cells in peripheral blood at different time points after transplantation of 1 × 106 transgene-positive cells (mean ± SEM of the indicated number of mice). #For mice that died before week 12, engraftment in peripheral blood is shown for the time point of death. (E) White blood cell count in peripheral blood from mice that received transplants of cells transduced with the indicated constructs. Blood was taken 4, 8, and 12 weeks after transplantation (mean ± SEM of the indicated number of mice). (F) Hemoglobin level in peripheral blood from mice that received transplants of cells transduced with the indicated constructs. Blood was taken 4, 8, and 12 weeks after transplantation (mean ± SEM of the indicated number of mice). (G) Platelet counts in peripheral blood from mice that received transplants of cells transduced with the indicated constructs. Blood was taken 4, 8, and 12 weeks after transplantation (mean ± SEM of the indicated number of mice). (H) Survival of mice that received transplants of cells transduced with the indicated constructs. Results from 3 independent experiments using independently transduced cells are shown. (I) Percentage of blast cells in bone marrow of moribund mice (mean ± SEM of the indicated number of mice). (J) Representative Wright-Giemsa–stained cytospin preparations of bone marrow cells from moribund mice (Scale bar: 25 µm in the upper panel; Scale bar: 10 µm in the lower panel). *P < .05; **P < .01; ns, not significant.

Mutant IDH1 induces a myeloproliferative-like disease in immortalized bone marrow cells. (A) Association of IDH1 mutations with expression levels of HOXA9 in adult AML patients up to 60 years of age (n = 457). Normalized expression levels of HOXA9 are shown for patients with wild-type IDH1 (gray bars) and mutant IDH1 (red bars), which were determined on an Affymetrix microarray with 2 different probes.31  (B) Protein expression of HoxA9-immortalized cells transduced with a CTL vector or with FLAG-tagged wild-type IDH1 or mutant IDH1 using an anti-FLAG antibody. β-actin was probed on the same blot as a loading control. (C) Ratio of R-2HG to S-2HG in cultured HoxA9 cells transduced with CTL, IDH1wt, or IDH1mut (mean ± SEM of 4 independently transduced cell lines). (D) Engraftment of transduced cells in peripheral blood at different time points after transplantation of 1 × 106 transgene-positive cells (mean ± SEM of the indicated number of mice). #For mice that died before week 12, engraftment in peripheral blood is shown for the time point of death. (E) White blood cell count in peripheral blood from mice that received transplants of cells transduced with the indicated constructs. Blood was taken 4, 8, and 12 weeks after transplantation (mean ± SEM of the indicated number of mice). (F) Hemoglobin level in peripheral blood from mice that received transplants of cells transduced with the indicated constructs. Blood was taken 4, 8, and 12 weeks after transplantation (mean ± SEM of the indicated number of mice). (G) Platelet counts in peripheral blood from mice that received transplants of cells transduced with the indicated constructs. Blood was taken 4, 8, and 12 weeks after transplantation (mean ± SEM of the indicated number of mice). (H) Survival of mice that received transplants of cells transduced with the indicated constructs. Results from 3 independent experiments using independently transduced cells are shown. (I) Percentage of blast cells in bone marrow of moribund mice (mean ± SEM of the indicated number of mice). (J) Representative Wright-Giemsa–stained cytospin preparations of bone marrow cells from moribund mice (Scale bar: 25 µm in the upper panel; Scale bar: 10 µm in the lower panel). *P < .05; **P < .01; ns, not significant.

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