The Runt-related transcription factor 1 (RUNX1): a gatekeeper in blood malignancies

The RUNX1 gene encodes a transcription factor capable of recognizing and binding a specific DNA sequence known as the Runt domain (5’-PyGPyGGT-3’) and found in many gene enhancers and promoters. It is a frequent target of genetic translocations and mutations in a variety of blood malignancies including acute and chronic leukemia. The current hypothesis suggests that loss or disruption of RUNX1 helps a certain subset of self-renewing stem cells escape from the control of homeostasis, and that mutations accumulating over time will occur and trigger the malignant phenotype characteristic of leukemia. In their publication in PLoS One, Dr. Xiongwei Cai and colleagues from the University of Pennsylvania demonstrated that although RUNX1-deficient cells displayed cell cycle delay and decreased apoptosis, the frequency of RUNX1-negative long-term repopulating hematopoietic stem cells (LT-HSCs) was barely affected in the young adult bone marrow. Looking further into the transcriptome of RUNX-1-deficient LT-HSCs, RNAs were extracted and labeled using Enzo’s BioArray® High Yield RNA transcript labeling kit for microarray analysis. Unique genes and pathways, involved notably in cell cycle and p53 signaling, were identified as being significantly affected by the loss of RUNX1. These results suggest that RUNX1 deficiency has very little impact on functional LT-HSCs, but instead allows the slow development of a small subset of HSCs in a pre-leukemic state which upon the acquisition of secondary mutations will ultimately lead to leukemia tumorigenesis.

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