Low-frequency TP53 hotspot mutation contributes to chemoresistance through clonal expansion in acute myeloid leukemia.

ABSTRACT: TP53 mutations (TP53mut) in AML patients associate with poor prognosis that may affect therapy and outcome. In addition to TP53 mut patients, TCGA AML patient sequencing data show that there are around 3% of patients have detectable low-frequency TP53mut reads. Importantly, these patients showed worse outcome as compared with the TP53 wild type (TP53wt) patients. We have studied the effect of low-frequency TP53mut in two AML cell lines, OCI-AML2 and MV4-11. Both cells have low-frequency single hotspot TP53mut. Interestingly, the resistant cells derived from both lines have homogeneous TP53mut. TP53mut clones isolated from the parental cells also show increased chemoresistance potential and have higher population of leukemia stem cell (LSC) maker positive cells, a characteristic of chemores

SUBMITTER: Yan B 

PROVIDER: S-EPMC7597970 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature