Targeted therapy in NPM1-mutated AML: Knowns and unknowns

Rong Wang; Pan Xu; Lin-Lin Chang; Shi-Zhong Zhang; Hong-Hu Zhu

doi:10.3389/fonc.2022.972606

Targeted therapy in NPM1-mutated AML: Knowns and unknowns

Front Oncol. 2022 Sep 27:12:972606. doi: 10.3389/fonc.2022.972606. eCollection 2022.

Authors

Rong Wang^{1

2}, Pan Xu³, Lin-Lin Chang³, Shi-Zhong Zhang³, Hong-Hu Zhu^{1

2

3

4

5

6}

Affiliations

¹ Department of Hematology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
² Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou, China.
³ Department of Physiology, Medical College of China Three Gorges University, Yichang, China.
⁴ Zhejiang University Cancer Center, Hangzhou, China.
⁵ Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China.
⁶ Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by malignant proliferation of myeloid hematopoietic stem/progenitor cells. NPM1 represents the most frequently mutated gene in AML and approximately 30% of AML cases carry NPM1 mutations. Mutated NPM1 result in the cytoplasmic localization of NPM1 (NPM1c). NPM1c interacts with other proteins to block myeloid differentiation, promote cell proliferation and impair DNA damage repair. NPM1 is a good prognostic marker, but some patients ultimately relapse or fail to respond to therapy. It is urgent for us to find optimal therapies for NPM1-mutated AML. Efficacy of multiple drugs is under investigation in NPM1-mutated AML, and several clinical trials have been registered. In this review, we summarize the present knowledge of therapy and focus on the possible therapeutic interventions for NPM1-mutated AML.

Keywords: AML; NPM1; XPO1 inhibitors; menin inhibitors; targeted therapy; venetoclax.

Publication types

Review