Fig. 1: miR-142 deficit induces BC-like transformation in the CP CML mouse. | Nature Communications

Fig. 1: miR-142 deficit induces BC-like transformation in the CP CML mouse.

From: Acquired miR-142 deficit in leukemic stem cells suffices to drive chronic myeloid leukemia into blast crisis

Fig. 1

a MiR-142 levels in bone marrow (BM) mononuclear cells (MNCs), CD34+ hematopoietic stem and progenitor cells (HSPCs), or CD34+CD38− hematopoietic stem cells (HSCs) from healthy individuals (normal; n = 14 biologically independent samples for MNCs and n = 8 for CD34+ and CD34+CD38−), chronic phase (CP) CML patients (n = 17 biologically independent samples for MNCs and n = 10 for CD34+ and CD34+CD38−), or blast crisis (BC) CML patients (n = 6 biologically independent samples for all three cell populations), analyzed by Q-RT-PCR. b MiR-142 levels in BM MNCs from miR-142−/− and miR-142+/+ mice (n = 12 each), analyzed by Q-RT-PCR. c Schematic design of the mouse crossings. Upon tetracycline withdrawal to induce BCR-ABL expression, miR-142−/−BCR-ABL, miR-142+/−BCR-ABL and miR-142+/+BCR-ABL mice were monitored for d white blood cell (WBC) counts (n = 20, 13 and 15 mice respectively) every two weeks, e blood (n = 4 mice per strain for blasts and n = 18 mice per strain for LSK) and f BM leukemic blasts (n = 4 mice per strain for blasts and n = 7 mice per strain for LSK) assessed by microscopy (left, scale bar: 10 µM) and Lin−Sca-1+c-Kit+ (LSKs) by flow cytometry (right), g spleen size and weight (left) and LSKs by flow cytometry (right) four weeks post BCR-ABL induction (n = 8 mice per strain). h Survival of miR-142−/−BCR-ABL (n = 17), miR−142+/−BCR-ABL (n = 10) and miR-142+/+BCR-ABL (n = 25) mice after BCR-ABL induction (Log-rank test, miR−142/−BCR-ABL vs miR-142+/−BCR-ABL: p = 0.004; miR-142+/−BCR-ABL vs miR-142+/+BCR-ABL: p = 0.007; miR-142−/−BCR-ABL vs miR-142+/+BCR-ABL: p < 0.0001). For a–h, source data are provided as a Source Data file. For e and f, results from one of the three independent experiments are shown (n = 3). Abbreviation: miR-142+/+B/A: miR-142+/+BCR-ABL; miR-142−/−B/A: miR-142−/−BCR-ABL; CP: chronic phase; BC: blast crisis. Comparison between groups was performed by two-tailed, unpaired t-test. Results shown represent mean ± standard error of the mean (SEM). Significance values: **p < 0.01; ****p < 0.0001; ns, not significant.

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