Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia.

In total, 3 HG3 WT,3HG3 TP53 MUT, 3 HG3-del(11q), 5 HG3del(11q) TP53 MUT, and 5 HG3-del(11q) ATM MUT TP53 MUT clones were generated. Interestingly,HG3-del(11q) ATM MUT TP53 MUT cellsfailedtoengraftandcompetewith HG3-del(11q) and HG3-del(11q) TP53 MUT cells, almost disappearingfrombothspleenandbonemarrow2weeks aftercellinjection(Figure4B). Datawerefittedinanexponential growthequation,andtimepointvaluesarepresentedasthemean±SEM.(C)RepresentativeimmunoblotanalysesofHG3 WT,HG3TP53 MUT, HG3-del(11q),HG3-del(11q)TP53 MUT,andHG3-del(11q)ATM MUT TP53 MUT wholecelllysates.ATM,PARP1,andCaspase-3proteinexpression and/orcleavagewereanalyzed. -actinwasusedasloadingcontrol.(D)CellcyclephasedistributionofHG3-editedcelllinesuponexposureto irradiationattheindicatedtimepoints. In addition, HG3 TP53 MUT, and HG3-del(11q) TP53 MUT cells showed a G2/M cell cycle arrest in accordance with TP53-defective cell-cycle phenotype, 37 which was also overcame 48 hours post-IR. [Extracted from the article]