Proleukemic RUNX1 and CBFβ Mutations in the Pathogenesis of Acute Leukemia

  • Michael E. Engel
  • Scott W. Hiebert
Part of the Cancer Treatment and Research book series (CTAR, volume 145)


The existence of non-random mutations in critical regulators of cell growth and differentiation is a recurring theme in cancer pathogenesis and provides the basis for our modern, molecular approach to the study and treatment of malignant diseases. Nowhere is this more true than in the study of leukemogenesis, where research has converged upon a critical group of genes involved in hematopoietic stem and progenitor cell self-renewal and fate specification. Prominent among these is the heterodimeric transcriptional regulator, RUNX1/CBFβ. RUNX1 is a site-specific DNA-binding protein whose consensus response element is found in the promoters of many hematopoietically relevant genes. CBFβ interacts with RUNX1, stabilizing its interaction with DNA to promote the actions of RUNX1/CBFβ in transcriptional control. Both the RUNX1 and the CBFβ genes participate in proleukemic chromosomal alterations. Together they contribute to approximately one-third of acute myelogenous leukemia (AML) and one-quarter of acute lymphoblastic leukemia (ALL) cases, making RUNX1 and CBFβ the most frequently affected genes known in the pathogenesis of acute leukemia. Investigating the mechanisms by which RUNX1, CBFβ, and their proleukemic fusion proteins influence leukemogenesis has contributed greatly to our understanding of both normal and malignant hematopoiesis. Here we present an overview of the structural features of RUNX1/CBFβ and their derivatives, their roles in transcriptional control, and their contributions to normal and malignant hematopoiesis.


Acute Myeloid Leukemia Normal Hematopoiesis Definitive Hematopoiesis Cytoplasmic Sequestration Central Nervous System Hemorrhage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors greatly appreciate the thoughtful comments and support from members of the Hiebert Laboratory during the preparation of this monograph.


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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Pediatric Hematology/OncologyDepartment of Pediatrics Monroe Carell Jr. Children’s Hospital at Vanderbilt and the Vanderbilt-Ingram Cancer CenterNashvilleUSA

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