Clonal Evolution Enhances Leukemia
Blackburn et al. report that some T cell acute lymphoblastic leukemia clones spontaneously evolve to obtain enhanced growth rate, leukemia-propagating potential, and chemotherapy resistance in the absence of therapy-induced selection. They find this is sometimes achieved by acquiring Akt pathway activation.
Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown molecular mechanisms. To address this issue, functional differences between single T-cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a ...
Clonal Evolution Enhances Leukemia
To address this issue, functional differences between single T cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model. Functional variation was observed within individual clones, with a minority of clones enhancing growth rate and leukemia-propagating potential with time.
Significance Uncovering the consequences of acquired mutations resulting from clonal evolution will be critical for understanding tumor progression and relapse. Our findings demonstrate that a subset of single T-ALL cells spontaneously acquired Akt pathway activation, which decreased latency, increased the frequency of relapse-driving leukemia-propagating cells (LPCs) and mediated resistance ...
Clonal evolution enhances leukemia
Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown molecular mechanisms. To address this issue, functional differences between single T cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model. Functional variation was observed within individual clones, with a minority of clones enhancing growth rate and leukemia ...
Here, a method is presented for creating primary, fluorescently-labeled T-cell acute lymphoblastic leukemia (T-ALL) in syngeneic zebrafish, and transplanting these tumors at limiting dilution into ...
Clonal evolution enhances leukemia propagating cell frequency in T
Functional differences between single T-cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model and Akt pathway activation was acquired in a subset of these evolved clones, which increased the number of leukemia propagating cells through activating mTORC1. SUMMARY Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown ...
Abstract. Leukemia progression and relapse are driven by molecularly distinct and often-rare cancer cells called leukemia-propagating cells (LPCs). If LPCs are retained following treatment, they will ultimately initiate relapse disease. Despite the substantial number of genetic lesions that have been identified in relapse samples and the contention that these mutations likely modulate response ...
