The overexpression of miR-130b and miR-128a in Mll-AF4⁺ FL LSK leads to a mixed/BCP/myeloid or lymphoblastic acute leukemia, respectively. (A) Experimental design. All mice received Mll-AF4–expressing cells. (B-C) Survival curve of primary, secondary, and tertiary recipients of the Mll-AF4⁺ pMIRH-130b (B) and Mll-AF4⁺ pMIRH-128a (C) cohorts. Total BM from 1 to 2 primary recipients was used for secondary transplants. Total BM from 2 to 3 recipients was used for tertiary transplants. Positive event = hematological malignancy linked to donor cells. A Gehan-Breslow-Wilcoxon test was used to compare survival curves. (D) Types of malignancies in Mll-AF4⁺ control, Mll-AF4⁺ pMIRH-130b, and Mll-AF4⁺ pMIRH-128a primary recipients. A χ² test was used to compare the distribution of sick and non-sick mice. (E) Postmortem pictures of sick mice from the Mll-AF4⁺ control, Mll-AF4⁺ pMIRH-130b, and Mll-AF4⁺ pMIRH-128a cohorts. (F-G)) Spleen (F) and liver (G) weights. (H) GFP chimerism in the BM. (I) White blood cell (WBC) counts in Mll-AF4⁺ control and sick mice. (J-N) Proportion of myeloid cells (J), mixed lineage cells (K), B-lymphoid cells (L), c-Kit⁺ cells (M), and IgM⁺ and Il7r⁺ cells (N) in the GFP⁺ fraction of the BM of Mll-AF4⁺ control and sick mice (Mll-AF4⁺ pMIRH-130b or Mll-AF4⁺ pMIRH-128a). (O) Proportion of LSK Il7r⁺Flt3⁻, HSCs/MPPs (LSK Il7r⁻ Flt3⁻), and LMPPs (LSK Flt3⁺) in the LSK compartment of control and sick mice. (P) CNS infiltration in Mll-AF4⁺ control, Mll-AF4⁺ pMIRH-130b, and Mll-AF4⁺ pMIRH-128a mice. The level of infiltration is described in “Methods.” (Q) Romanowsky staining of peripheral blood smears; scale bars, 20 μm. Data were compared using a Mann-Whitney U test. *P < .05; **P < .01; ***P < .001; ****P < .0001. Graphs are presented as mean ± standard error of the mean (1 dot = 1 mouse).