Aberrant epigenetic regulators control expansion of human CD34+ hematopoietic stem/progenitor cells

Abstract

Transcription is a tightly regulated process ensuring the proper expression of numerous genes regulating all aspects of cellular behavior. Transcription factors regulate multiple genes including other transcription factors that together control a highly complex gene network. The transcriptional machinery can be “hijacked” by oncogenic transcription factors, thereby leading to malignant cell transformation. Oncogenic transcription factors manipulate a variety of epigenetic control mechanisms to fulfill gene regulatory and cell transforming functions. These factors assemble epigenetic regulators at target gene promoter sequences, thereby disturbing physiological gene expression patterns. Retroviral vector technology and the availability of “healthy” human hematopoietic CD34+ progenitor cells enable the generation of pre-leukemic cell models for the analysis of aberrant human hematopoietic progenitor cell expansion mediated by leukemogenic transcription factors. This review summarizes recent findings regarding the mechanism by which leukemogenic gene products control human hematopoietic CD34+ progenitor cell expansion by disrupting the normal epigenetic program.

The immunogenetics of Psoriasis: A comprehensive review

“…There are also psoriasis-associated mutations in RUNX1 , another transcription factor in the Runt-domain containing family [18]. RUNX1 plays an important role in normal hematopoiesis and has mainly been investigated regarding its’ dysregulation in leukemia and other hematopoietic cancers [40]. RUNX1 is expressed in naïve CD4+ T-cells and is rapidly downregulated upon TCR stimulation [39].…”

51. Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI), Lübeck, 19.-21. September 2018, Abstracts

“…Despite the description of multiple local factors, which support self-renewal within the niche, it has not been possible to establish similar conditions in ex vivo CD34+ progenitor cultures, so far. Of note, a few leukemia-related transcription factors were recently shown to confer remarkable ex vivo expansion capacity in progenitor cells (Faridi et al:, 2013). Methods: The coding sequences (CDS) of chemically inducible-engineered transcription factors derived from RUNX1 and MLL fusion genes were retrovirally transduced into and expressed in human CD34+ progenitors.…”