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Tumor Discovery

REVIEW ARTICLE
FBXW7 in leukemia: A critical regulator of

oncogenic stability and a potential therapeutic
target

Xiuming Li and Bin Liu*

Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy,
Jiangsu Ocean University, Lianyungang, Jiangsu, China
(This article belongs to the Special Issue: Advances in Tumor Immune Regulation: Mechanisms and
Therapeutic Insights)

Abstract

F-Box and WD repeat domain-containing 7 (FBXW7) is a key tumor suppressor
and substrate-recognition component of the Skp1-Cullin-F-box E3 ubiquitin
ligase complex, responsible for targeting several crucial oncogenic proteins for
proteasomal degradation. It plays a significant role in preventing the accumulation
of pro-oncogenic substrates, thereby maintaining cellular homeostasis. Mutations
or inactivation of FBXW7 disrupt these processes, leading to the stabilization of
oncogenic proteins such as c-Myc, Notch, myeloid cell leukemia 1, and cyclin E,
which drive malignant transformation in several cancers, including hematological
malignancies such as T-cell and B-cell acute lymphoblastic leukemia. These mutations
contribute to resistance to apoptosis, dysregulated proliferation, and poor prognosis,
*Corresponding author:
Bin Liu highlighting FBXW7 as a critical factor in leukemia pathogenesis and a promising
(liubin@jou.edu.cn) therapeutic target. Here, we review FBXW7’s structure and function, its key substrates
Citation: Li X, Liu B. FBXW7 in in leukemia, and therapeutic strategies that restore its function or target the oncogenic
leukemia: A critical regulator of pathways it regulates. Advances in genome-wide CRISPR screenings and proteomics
oncogenic stability and a potential have further illuminated FBXW7’s involvement in multidrug resistance, positioning it
therapeutic target. Tumor Discov.
2025;4(3):1-15. as a biomarker and therapeutic target for improving leukemia treatment outcomes.
doi: 10.36922/TD025150027
Received: April 11, 2025 Keywords: F-Box and WD repeat domain-containing 7; Leukemia; Ubiquitin-proteasome
Revised: May 16, 2025 pathway; c-Myc; Notch; Myeloid cell leukemia 1; Tumor suppressor; Therapeutic target
Accepted: May 20, 2025
Published online: June 6, 2025
1. Introduction
Copyright: © 2025 Author(s).
This is an Open-Access article 1.1. Overview of leukemia
distributed under the terms of the
Creative Commons Attribution Leukemia is a highly heterogeneous hematologic malignancy, characterized by the
License, permitting distribution,
1
and reproduction in any medium, abnormal proliferation of leukemia cells in the hematopoietic system. These cells
provided the original work is lose normal regulation of proliferation and differentiation. This condition often arises
properly cited. from clonal genetic mutations in hematopoietic stem or progenitor cells, which cause
2
Publisher’s Note: AccScience these cells to transform into leukemia cells under uncontrolled conditions. Genetic
Publishing remains neutral with mutations, chromosomal aberrations, and epigenetic alterations not only grant leukemia
regard to jurisdictional claims in
published maps and institutional cells abnormal proliferative capacity but also lead to the loss of normal differentiation
3
affiliations. function. As a result, these cells remain in an undifferentiated or poorly differentiated

Volume 4 Issue 3 (2025) 1 doi: 10.36922/TD025150027