Molecular Basis and Targeted Inhibition of CBFβ-SMMHC Acute Myeloid Leukemia

被引：3

作者：

Castilla, Lucio H. ^{[1
]}

Bushweller, John H. ^{[2
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA 01605 USA

[2] Univ Virginia, Sch Med, Mol Physiol & Biophys, Charlottesville, VA 22908 USA

来源：

RUNX PROTEINS IN DEVELOPMENT AND CANCER | 2017年 / 962卷

关键词：

CBF; CBFb-MYH11; CBFbeta-SMMHC; RUNX1; AML; inv(16); Leukemia; AI-10-49; Targeted therapies; Protein-protein interaction inhibitor; PPI; ACUTE MYELOMONOCYTIC LEUKEMIA; MYOSIN HEAVY-CHAIN; ACUTE MYELOGENOUS LEUKEMIA; FETAL LIVER HEMATOPOIESIS; BINDING-FACTOR LEUKEMIA; STEM-CELLS; TRANSCRIPTION FACTORS; SMOOTH-MUSCLE; FUSION GENE; PHILADELPHIA-CHROMOSOME;

D O I：

10.1007/978-981-10-3233-2_15

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myeloid leukemia (AML) is characterized by recurrent chromosomal rearrangements that encode for fusion proteins which drive leukemia initiation and maintenance. The inv(16)(p13q22) rearrangement is a founding mutation and the associated CBF beta-SMMHC fusion protein is essential for the survival of inv(16) AML cells. This Chapter will discuss our understanding of the function of this fusion protein in disrupting hematopoietic homeostasis and creating pre-leukemic blasts, in its cooperation with other co-occurring mutations during leukemia initiation, and in leukemia maintenance. In addition, this chapter will discuss the current approaches used for the treatment of inv(16) AML and the recent development of AI-10-49, a selective targeted inhibitor of CBF beta-SMMHC/RUNX1 binding, the first candidate targeted therapy for inv(16) AML.

引用

页码：229 / 244

页数：16

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