Fig. 5: Single treatment of DOR and dual treatments of BMP inhibitors and IM inhibit cell proliferation of CML CD34+ cells. | Cell Death & Disease

Fig. 5: Single treatment of DOR and dual treatments of BMP inhibitors and IM inhibit cell proliferation of CML CD34+ cells.

From: Chronic myeloid leukaemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal

Fig. 5Fig. 5

a, b CellTrace™ Violet (CTV) proliferation analysis of normal and CP-CML CD34+ cells treated with IM, BMP inhibitors, the combination (IM = 1μM, LDN = 1 μM, DOR = 2.5 μM, n = 3), in absence or presence of BMP4 at 72 h. i Results for normal CD34+ cells display that single and dual treatment of IM + DOR inhibit cell proliferation, and additional BMP4 treatment (b) results in more cell divisions compared to standard culture conditions without BMP4. a-ii Proliferation analysis of CP-CML samples indicates that LDN in combination with IM synergistically inhibits proliferation compared to single treatment. DOR alone and in combination with IM displays the biggest fold change compared to NDC. Additional treatment with BMP4 (b-ii) did not reveal differences in proliferation progression compared to standard culture conditions. c IM and BMP inhibitors reduce CD34+ cell numbers in CP-CML samples in absence or presence of BMP4. Results are displayed as median range of CD34+ cell numbers of normal and CP-CML CD34+ cells treated with IM, BMP inhibitors and the combination (IM = 1 µM, LDN = 1 µM, DOR = 2.5 μM, n = 3) in absence or presence of BMP4. d-i CFC assay results of normal CD34+ cells treated with IM, BMP inhibitors and the combination of (IM = 1 µM, LDN = 1 µM, DOR = 2.5 μM) do not reveal any significant difference compared to NDC (n = 3). ii Total number of colonies of CP-CML CD34+ cells display a significant difference across all treatments compared to NDC and a synergistic reduction when IM and DOR were used in combination (n = 3). iii CFC results of K562 cells. Results also indicate a significant drop in the number of colonies with IM, DOR and LDN. Results are also reflected in the morphology of the colonies with DOR and LDN treatment reducing the size of colonies (n = 3). Data are expressed as mean ± standard deviation and were compared using ANOVA (c) and the unpaired Student’s t-test (a, b, d), ***p < 0.001–0.0001, **p < 0.01–0.001, *p < 0.05–0.01

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