The emerging role of Twist proteins in hematopoietic cells and hematological malignancies

N Merindol,N Bonnefoy,V Szablewski,A Puisieux,A Riquet,J-F Eliaou

doi:10.1038/bcj.2014.22

Abstract

Twist1 and Twist2 (Twist1–2) are two transcription factors, members of the basic helix-loop-helix family, that have been well established as master transcriptional regulators of embryogenesis and developmental programs of mesenchymal cell lineages. Their role in oncogenesis in epithelium-derived cancer and in epithelial-to-mesenchymal transition has also been thoroughly characterized. Recently, emerging evidence also suggests a key role for Twist1–2 in the function and development of hematopoietic cells, as well as in survival and development of numerous hematological malignancies. In this review, we summarize the latest data that depict the role of Twist1–2 in monocytes, T cells and B lymphocyte activation, and in associated hematological malignancies.

Highlights

Twist[1,2] main functionsTwist[1] and Twist[2] (Twist1–2) are two distinct tissue-restricted transcription factor members of the basic helix-loop-helix class B family that display high sequence similarity with each other
Mutations in twist[1] cause the Saethre–Chotzen syndrome, an autosomal dominant inheritance disease principally characterized by craniosynostosis.[1,2]
Mutations in twist[2] are associated with the Setleis Syndrome, an inherited developmental disorder characterized by bilateral temporal marks and other facial features.[7]

Summary

INTRODUCTION

Twist[1] and Twist[2] (Twist1–2) are two distinct tissue-restricted transcription factor members of the basic helix-loop-helix (bHLH) class B family that display high sequence similarity with each other. They play a critical role in embryogenesis, in the inhibition of mesenchymal cell development. Twist[2] inhibits terminal differentiation of mesoderm-derived cells, such as myocytes, osteoblasts and adipocytes.[3,4,5,6] In humans, mutations in twist[2] are associated with the Setleis Syndrome, an inherited developmental disorder characterized by bilateral temporal marks and other facial features.[7] Twist2ko mice exhibit normal embryogenesis but die 2–3 days after birth of generalized cachexia caused by high levels of proinflammatory cytokines.[8]. Twist[1,2] partner choice depends mostly on its accessibility and on Twist[1,2] phosphorylation acetylation

TTFF Rep

Cellular proliferation Resistance to chemotherapy

Myeloid malignancies

Findings

CLL subtypes