Figure 3.
ETV6-NCOA2 collaborates with NOTCH1 to induce T/myeloid leukemia in human CD34+ progenitors. Human cord blood CD34+ progenitors were co-transduced with MSCV-MIGR1-IRES retroviruses that express EN2-NGFR and NOTCH1-L1601PdP-GFP. (A) The cotransduction generated 4 groups of human cells that were cotransplanted into NSGS recipient mice (n = 15): (1) EN2, (2) NOTCH1-L1601PdP, (3) EN2 + NOTCH1-L1601PdP, and (4) untransduced CD34+ cells; right: examples of 2 mice, one with EN2 engraftment and the other with EN2 + NOTCH1-L1601PdP Log-rank (Mantel-Cox) (N) engraftment. (B) Kaplan-Meier tumor-free survival for primary and secondary mice by postmortem engraftment analysis (EN2 vs EN2 + NOTCH1-L1601PdP; P = .0004). (C) Summary of EN2 and EN2 + NOTCH1-L1601PdP immunophenotype CD33/CD7 (left) and cytMPO/cytCD3 (right) (Mann-Whitney U test; **P = .0087). Panel C represents the percentage of positive cells out of the CD45+ population. Each dot represents a mouse. (D) Examples of flow cytometry analysis of EN2-NGFR and EN2 + NOTCH1-L1601PdP-GFP, CD34/CD38, CD7/CD33, CD19/CD33, and cytCD3/cytMPO. Cyt, cytoplasmic; ns, not significant.