Title

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

UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network

Publication Date

2017-03-16

Document Type

Article

Disciplines

Biochemistry | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

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 CBFbeta-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 CBFbeta-SMMHC/RUNX1 binding, the first candidate targeted therapy for inv(16) AML.

Keywords

AI-10-49, AML, CBF, CBFb-MYH11, CBFbeta-SMMHC, Leukemia, PPI, Protein-protein interaction inhibitor, RUNX1, Targeted therapies, inv(16)

DOI of Published Version

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

Source

Adv Exp Med Biol. 2017;962:229-244. doi: 10.1007/978-981-10-3233-2_15. Link to article on publisher's site

Journal/Book/Conference Title

Advances in experimental medicine and biology

Related Resources

Link to Article in PubMed

PubMed ID

28299661

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