Gene set–based decomposition of T-ALL with respect to normal T-cell implies two distinct T-ALL progression pathways

In this investigation a gene set–based approach is used to compare T-ALL samples to a series of chronologically ordered T-cell development stages. These results revealed two distinct subtypes of T-ALL that can be de?ned by different cells of origin; either a multipotent hematopoietic stem cell, or a committed T-cell. Subsequently, two-step progression pathways in terms of biological process perturbations were determined for each of these subtypes based on differentially expressed gene sets. The two-step model allowed the characterization of a novel cell type, the T-ALL stem cell. The results indicate that T-ALL can emerge from both multipotent cells as well as committed T-cells, and that the progression pathways of each of these subtypes proceeds via different T-ALL stem cells.