Bcr-Abl is a "molecular switch" for the decision for growth and differentiation in hematopoietic stem cells.
Chronic myeloid leukemia (CML) is a clonal disorder originating in the pluripotent hematopoietic stem cell (HSC), the hallmark of which is the constitutively activated p210-type of Bcr-Abl tyrosine kinase protein. Studies in recent years have helped us to understand the molecular processes involved in the initiation and progression of CML. Although a great amount of knowledge has been accumulated, the effect of Bcr-Abl on the HSC is still unclear. We have developed an in vitro system that mirrors the chronic phase of CML with a combination of in vitro embryonic stem cell differentiation and tetracycline-inducible Bcr-Abl expression. Enforced Bcr-Abl expression was sufficient to increase the number of both multilineage progenitors and myeloid progenitors. The current system is powerful for analyzing the genetic changes in hematopoietic development. This review focuses on how Bcr-Abl affects HSCs and how Bcr-Abl expression alters the properties of HSCs.
Era
Takumi
T
Stem Cell Biology Group, RIKEN Center for Development Biology, Kobe City, Hyogo, Japan. tera@cdb.riken.go.jp
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology
D016044:Fusion Proteins, bcr-abl; D013752:Tetracycline