BioProject

Increased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. More...

Increased expression of Kruppel like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7-/- cells was comparable to control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, while resulting in multi-lineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21Cip1/Waf1) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor (HSPC) function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival. KLF7 overexpression in HSPCs expression array: Lin- c-Kit+ Sca-1+ cells transduced with a KLF7 expressing or control (empty vector) lentivirus. Expression profiles of KLF7 overexpressing vs controls HSPCs. Overall design: Cells were harvested 72 hrs post-transduction to compare expression profiles of control vs KLF7 overexpressing HSPCs Less...