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. 2018 Feb 8;10(3):1115–1130. doi: 10.1016/j.stemcr.2018.01.015

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© 2018 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMC Copyright notice

ADAM8 Marks TKI-Resistant CML Cells in BM Samples of Patients with Newly Diagnosed CML-CP

(A) A scheme of viability and apoptosis assay for ADAM8+ cells in CD34 + stem/progenitor fraction.

(B) Viability assay for CD34+/ADAM8+ cells in BM of newly diagnosed CML-CP patients. Data show means ± SEM, n = 6 patients (p values: two-tailed Student's t test; ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001).

(C) Apoptosis assay for CD34+/ADAM8+ cells in BM of newly diagnosed CML-CP patients. Representative FCM data are shown on the left; 2.5 μM imatinib for 48 hr, which significantly induces apoptosis in ADAM8− cells, does not induces apoptosis in ADAM8+ cells. Data show means ± SEM, n = 4 patients (p values: two-tailed Student's t test; ^∗p < 0.05).

(D) Frequency of ADAM8+ cells in CD34+/CD38+ progenitor fraction and CD34+/CD38−stem cell fraction. In the progenitor fraction, the frequency of ADAM8+ cells is significantly higher in CML-CP patients (n = 18) than in non-Hodgkin lymphoma (n = 3) and other hematological malignancies (AML, n = 1; acute lymphocytic leukemia, n = 1; myelodysplastic syndrome, n = 1; chronic myelomonocytic leukemia, n = 3). Data show means ± SEM, n = shown above patients (p values: two-tailed Student's t test; ^∗p < 0.05).

(E) A scheme of viability and apoptosis assay for ADAM8+ cells in CD34+/CD38+ stem/progenitor fraction.

(F) Viability assay for CD34+/CD38+/ADAM8+ cells in BM of newly diagnosed CML-CP patients. Data show means ± SEM, n = 4 patients (p values: two-tailed Student's t test; ^∗p < 0.05).

(G) Apoptosis assay for CD34+/CD38+/ADAM8+ cells in BM of newly diagnosed CML-CP patients. Representative FCM data are shown on the left; 2.5 μM imatinib for 48 hr, which significantly induces apoptosis in ADAM8− cells, does not induce apoptosis in ADAM8+ cells. Data show means ± SEM, n = 6 patients (p values: two-tailed Student's t test; ^∗p < 0.05).