Restoring p53-wild type conformation in TP53-Y220C mutant acute myeloid leukemia

Bing Z. Carter

doi:10.1182/blood.2025028935

Restoring p53-wild type conformation in TP53-Y220C mutant acute myeloid leukemia

2025-07-05

0

PRE

AI

B

Bing Z. Carter *

P

Po Yee Mak

E

Edward Ayoub

X

Xiaogang Wu

B

Baozhen Ke

Y

Yuki Nishida

P

P. Andrew Futreal

L

Lauren B. Ostermann

A

Andrea Bedoy

S

Steffen Boettcher

C

Courtney D. DiNardo

A

Anna M. Puzio‐Kuter

M

Masha V. Poyurovsky

A

Arnold J. Levine

M

Michael Andreeff *

DOI：10.1182/blood.2025028935

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Abstract

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• PC14586 refolds Y220C-mutant p53 into a wild-type (WT)-like conformation and activates p53 targets but induces limited cell death in AML • We identified factors limiting the apoptogenic efficacy of the refolded p53-WT, which can be enhanced by co-targeting MDM2, XPO1, or BCL-2

Keywords:

PC14586

Y220C-mutant p53

wild-type-like conformation

p53 targets

cell death

MDM2

XPO1

BCL-2

Restoring p53-wild type conformation in TP53-Y220C mutant acute myeloid leukemia

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