Synapse
⌘+K
Synapse
PulseExploreClubsResearchersJournals
Instagram
HomeClubsExplore
December 8, 2025Blood

Targeting TP53 promotes anti-leukemia immunity and enhances CD70 CAR-T efficacy in AML by transcriptionally upregulating CD70

View Full Paper
Ask AI
Bookmark
Share

Authors

YSYuan SongYLYun LiKBKaranpreet Singh Bhatia

Discussion

Loading...

Member takes

Overview

Genome-wide CRISPR screen identifies TP53 as a transcriptional regulator of CD70, suggesting it improves immunotherapy in AML.

Key Points

  • This research focuses on the role of TP53 in regulating CD70 expression and its implications for CAR-T therapy in acute myeloid leukemia (AML).
  • Conducted a genome-wide CRISPR knock out screen in myeloid leukemia cells to identify regulators of CD70.
  • Validated findings in isogenic AML cell lines with different TP53 statuses.
  • Analyzed RNA-seq data from primary AML samples and cell lines to assess CD70 expression relative to TP53.
  • Performed chromatin immunoprecipitation sequencing to investigate p53 binding at the CD70 locus.
  • Tested the efficacy of CD70-overexpressing CAR-T cells in mouse models of AML.
  • TP53 was identified as a positive regulator of CD70 expression, with mutations reducing CD70 levels.
  • p53 activation via Nutlin and chemotherapy upregulated CD70 in TP53-wild-type cells.
  • CD70 overexpression impaired leukemia growth in immunocompetent mice, indicating it activates NK cell-mediated immunity.
  • CLinical samples showed higher CD70 expression in TP53 wild-type AML, correlating with better outcomes post-chemotherapy.

Cite This Study

Song et al. (2025) studied this question.

synapsesocial.com/papers/69362f3d4fa91c937236d498https://doi.org/10.1182/blood-2025-2349
View Full Paper
Ask AI
Bookmark
Share