Reprogramming of B cell acute lymphoblastic leukemia cells: Do we need to shoot a moving target?

In a recent paper, McClellan et al. (1) report that blasts from some precursor B cell acute lymphoblastic leukemia (B-ALL) cases transdifferentiate (reprogram) into nonmalignant cells. Although showing induced reprogramming in both Philadelphia chromosome-positive (Ph+) and Ph− cases, the authors concentrate on Ph+ leukemias, proposing reprogramming to be a possible therapeutic modality for this high-risk group of B-ALLs. Although the findings are highly interesting and relevant, we would like to raise several points of concern. The authors report that reprogrammed cells resemble normal macrophages based on mostly descriptive observations. Importantly, the authors claim that those differentiated cells lose leukemogenicity based on xenotranplantation experiments. …