Figure 2
Figure 2. BMPRIb is specifically deregulated in primary immature CD34+ CML cells. Comparative expression of BMPRIa (A) and BMPRIb (B) genes in distinct sorted subpopulations obtained from healthy donor BM samples (n = 4; open bars) and CP-CML patient samples at diagnosis (n = 3; closed bars). The subpopulations represent immature primitive cells (C34+CD38−), immature progenitors (C34+CD38+), lineage-restricted progenitors (C34−CD38+), monocytes/granulocytes (CD14/CD15+), mature myeloid cells (CD33+), megakaryocytes (CD61/CD41+), erythroid compartments (glycophorin A-GPA+), and T (CD3+) and B (CD19+) lymphocytes. Results are expressed as fold change vs the reference value for each gene, using the same healthy donor sample. *P < .05, **P < .005, and ***P < .0001 indicate differences between the gene expression levels in CML compared with healthy samples. (C) Comparative expression of Bmi1, BMPRIa, and BMPRIb genes in CD34+ and CD34− cells obtained from healthy donors (n = 14; open bars) and CML patient samples either in chronic phase (CP) at diagnosis (n = 53; gray bars) or in advanced (Adv) phase at diagnosis (n = 4; closed bars). Results from patient samples in CP at diagnosis are subdivided between low (<0.8), intermediate (0.8–1.2), and high (> 1.2) Sokal scores (different tone gray bars). (D) Flow cytometry analysis of BMPRIa and BMPRIb cell surface expression in CD34+ and CD34− cells obtained from healthy donors (n = 9; open bars) and CP-CML samples at diagnosis (n = 14; closed bars), using a FACSCalibur cell analyzer (Becton Dickinson). Results are expressed as the percentage of receptor-expressing cells. *P < .05 indicates differences between healthy and CML samples. Comparative expression of (E) ABL, BCR-ABL and Bmi1 genes or (F) BMPRIa and BMPRIb genes by qPCR in parental TF1 cells transduced either with an empty vector (non-BCR-ABL; open bars) or with a vector containing BCR-ABL expressing sequence (closed bars). Results represent the mean value ± standard error of the mean (SEM) of 7 (E) or 14 experiments (F). *P < .05 indicates differences between parental TF1 cells transduced with an empty vector and BCR-ABL-transduced TF1 cells. (G) Flow cytometry analysis of BMPRIb receptor cell surface expression on either parental TF1 cells transduced with an empty vector (non-BCR-ABL; open bars) or with a vector containing BCR-ABL expressing sequence (closed bars) and, as indicated, performed on viable cells using a FACSCalibur cell analyzer (Becton Dickinson). Results represent the mean value ± SEM of 8 experiments. **P < .005 indicates differences between parental TF1 cells transduced with an empty vector and BCR-ABL-transduced TF1 cells.

BMPRIb is specifically deregulated in primary immature CD34+CML cells. Comparative expression of BMPRIa (A) and BMPRIb (B) genes in distinct sorted subpopulations obtained from healthy donor BM samples (n = 4; open bars) and CP-CML patient samples at diagnosis (n = 3; closed bars). The subpopulations represent immature primitive cells (C34+CD38−), immature progenitors (C34+CD38+), lineage-restricted progenitors (C34−CD38+), monocytes/granulocytes (CD14/CD15+), mature myeloid cells (CD33+), megakaryocytes (CD61/CD41+), erythroid compartments (glycophorin A-GPA+), and T (CD3+) and B (CD19+) lymphocytes. Results are expressed as fold change vs the reference value for each gene, using the same healthy donor sample. *P < .05, **P < .005, and ***P < .0001 indicate differences between the gene expression levels in CML compared with healthy samples. (C) Comparative expression of Bmi1, BMPRIa, and BMPRIb genes in CD34+ and CD34− cells obtained from healthy donors (n = 14; open bars) and CML patient samples either in chronic phase (CP) at diagnosis (n = 53; gray bars) or in advanced (Adv) phase at diagnosis (n = 4; closed bars). Results from patient samples in CP at diagnosis are subdivided between low (<0.8), intermediate (0.8–1.2), and high (> 1.2) Sokal scores (different tone gray bars). (D) Flow cytometry analysis of BMPRIa and BMPRIb cell surface expression in CD34+ and CD34− cells obtained from healthy donors (n = 9; open bars) and CP-CML samples at diagnosis (n = 14; closed bars), using a FACSCalibur cell analyzer (Becton Dickinson). Results are expressed as the percentage of receptor-expressing cells. *P < .05 indicates differences between healthy and CML samples. Comparative expression of (E) ABL, BCR-ABL and Bmi1 genes or (F) BMPRIa and BMPRIb genes by qPCR in parental TF1 cells transduced either with an empty vector (non-BCR-ABL; open bars) or with a vector containing BCR-ABL expressing sequence (closed bars). Results represent the mean value ± standard error of the mean (SEM) of 7 (E) or 14 experiments (F). *P < .05 indicates differences between parental TF1 cells transduced with an empty vector and BCR-ABL-transduced TF1 cells. (G) Flow cytometry analysis of BMPRIb receptor cell surface expression on either parental TF1 cells transduced with an empty vector (non-BCR-ABL; open bars) or with a vector containing BCR-ABL expressing sequence (closed bars) and, as indicated, performed on viable cells using a FACSCalibur cell analyzer (Becton Dickinson). Results represent the mean value ± SEM of 8 experiments. **P < .005 indicates differences between parental TF1 cells transduced with an empty vector and BCR-ABL-transduced TF1 cells.

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