Single-cell transcriptomic and phylogenetic analyses reveal new insights into the developmental origin and potential therapeutic targets for a particularly aggressive form of B-cell acute lymphoblastic leukemia in infants. ChildhoodCancerAwarenessMonth
. We directly determined the phylogenetic origin of an infant leukemia in a rare case of a child in whom infant B-ALL and childhood AML developed, both harboringKMT2A
rearrangement arose before gastrulation and specification of hematopoiesis. With the important caveat that this case will not represent allrearranged B-ALL, it demonstrates that the cell of origin cannot be inferred from the transcriptional phenotype of leukemia cells.
The quantitative molecular approach we deployed here, leveraging large archives of bulk mRNAs, emerging reference catalogs of normal human cells and direct examination of single blast transcriptomes, lends itself for reappraising the phenotype of human leukemias to derive novel biological and therapeutic hypotheses.
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