miR-126 Bioactivity Marks the Functional LSC Compartment in Human AML
(A) Schematic describing the sorting scheme/scoring system for secondary mice. AML samples were transduced with an miR-126 reporter construct and transplanted into conditioned NSG mice for 12 weeks. Bone marrow was analyzed for engraftment using CD45+ΔNGFR+EGFP+ staining. Cells were sorted into four populations based on ΔNGFR (transduced cells) and EGFP expression (inverse of miR-126 bioactivity), counted, and injected into secondary mice for 8–10 weeks. When a ΔNGFR/EGFP profile is recapitulated in secondary mice, the mouse is scored as engrafted.
(B) Summary of the results of the miR-126 bio-reporter assays.
(C) Kaplan-Meier overall survival (OS) curves in the PMCC CN AML cohort (n = 74) according to the miR-126 expression level (HR, 2.23; p = 0.00901).
(D) Univariate Cox model analysis for miR-126 as prognostic for event-free survival in the PMCC cohort of CN AML patients (n = 74; p = 0.0207, log rank test, median split; HR, 1.8744; p = 0.0207, Wald test).
(E) Kaplan-Meier survival curves correlating miR-126 expression and relapse-free survival in the PMCC patient cohort. Univariate median split log rank test (HR, 1.7995; p = 0.033, Wald test).
(F) Univariate analysis for OS in the TGCA AML cohort that encompasses all levels of cytogenetic risk (n = 187) according to the miR-126 expression level (HR, 1.41; p = 0.0382). See also Figure S2.