Submitted September 8, 2008
Accepted November 7, 2008
In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia
Manuela Germeshausen*, Karl Welte, and Matthias Ballmaier
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
* Corresponding author; email: germeshausen.manuela{at}mh-hannover.de.
Severe congenital neutropenia (CN) is a rare bone marrow failure syndrome with a high incidence of acute leukemia. In previous studies we could show that point mutations in the gene for the granulocyte colony-stimulating factor receptor CSF3R are a highly predictive marker for leukemic development in CN patients. In order to find out at which stage of hematopoietic development these mutations emerge and how they are propagated during hematopoietic differentiation we analyzed single cells of different hematopoietic subpopulations from CN patients with CSF3R mutations. We found that CSF3R mutations are not restricted to the myeloid compartment but are also detectable in lymphoid cells, whereas in a much lower percentage. From our observations we conclude that CSF3R mutations are acquired in multipotent hematopoietic progenitor cells in CN patients and that they are clonally expanded in myeloid cells expressing the G-CSF receptor due to the growth advantage mediated by the CSF3R mutation.
