Figure 5. The presence of FLT3-ITD and mutated NPM1 in ALDH^bright CD34+CD38− progenitor populations.

(A) In CD34-negative AML cases, the ALDH^bright population of AML cells consists, besides CD34+CD38− stem cells of CD38dim and CD38+ progenitors (A, middle panel, AML-464) (Table S3). The complete ALDH^bright compartment in CD34-negative AML has a normal phenotype as proven by the absence of FLT3-ITD in the CD34+CD38− (A, right upper panel) as well as the CD38dim (A, right middle panel) and CD38+ (data not shown) population of cells. The ALDH^low compartment contains the FLT3-ITD (arrow in right lower panel), indicating leukemic cells. (B) In CD34-positive AML cases, the ALDH^bright population contains, apart from normal CD34+CD38− HSC, CD34+CD38+ progenitors and CD34− cells (Figure 5B middle panel)(Table S3). The ALDH^bright CD34+CD38− stem cells lack molecular aberrancies (B, right upper two panels) and are therefore normal. The CD34+CD38+ progenitor compartment (B, right middle two panels) in this case has very small FLT3-ITD and NPM1 mutant peaks likely originating from purification of ALDH^low cells within the ALDH^bright compartment. The ALDH^low compartment is largely neoplastic (B, right lower 2 panels).