Fig. 7: Cell-of-transformation model for BCR-ABL1 lymphoblastic leukemia subtypes.
From: Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia
The disease originates from the rearrangement of BCR-ABL1 in a multipotent stem cell (HSC or MPP), which is the cell-of-origin. BCR-ABL1 increases cell proliferation and impairs DNA damage response. It then transforms by acquiring cooperating alterations in a downstream B-cell progenitor, which is the cell-of-transformation. Transformation-related events are mostly generated by RAG-mediated recombination. Inactivation of B-cell transcription factors and tumor suppressors causes a block in differentiation and evasion of programmed cell death, respectively. The molecular subtypes of BCR-ABL1 lymphoblastic leukemia arise from different target cells of transformation.
