Hematopoietic transformation in the absence of MLL1/KMT2A: distinctions in target gene reactivation

Figures & data

Figure 1. MLL1 is dispensable for leukemia initiation.

(a) Scheme using conditional Mll1 allele to test the role of endogenous MLL1 in the initiation of MLL-AF9-transformed leukemia cells. (b) Kaplan-Meier survival curve of recipient animals engrafted with MLL-AF9-transduced cells of the indicated genotypes (n = 9 per genotype). (c) Comparable number of blasts (% YFP+ cells in the peripheral blood) between Mll1^Δ/+ and Mll1^Δ/Δ groups. Bars indicate averages ± SD. (d) Genomic PCR with bone marrow cells from the moribund mice. (e) Serial replating of MLL-AF9-transduced bone marrow cells with or without Mll1 deletion. Five hundred cells were replated, and CFUs were scored in triplicate every 7 d. Bars indicate averages of triplicate cultures ± SD. (f) Genomic PCR with in vitro transformed cells from the end of the fourth replating.

Figure 2. Mll1 loss affects target gene expression before the initiation of MLL-AF9 leukemia.

(a) Scheme using Mll1 conditional knockout allele to test the role of endogenous MLL1 in maintaining target gene expression during the initiation of MLL-AF9 leukemia. (b-c) qRT-PCR of selected target genes 48 h after initiating Mll1 deletion (b) and fully transformed MLL-AF9 leukemia cells from day 31 after transplantation (c). (d) Also at day 31, YFP-sorted cells were plated on M3434 and clones expanded for 7 d. Clones (12 for each genotype) were picked and processed for qRT-PCR detection of the indicated target genes. Clones with undetectable Ct values are labeled as 0 on the plot.