Inherited biallelic CSF3R mutations in severe congenital neutropenia

In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia.

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 (G-CSF) receptor CSF3R are a highly predictive marker for leukemic development in CN patients. To find out at which stage of hematopoietic development these mutations e...

GM-CSF stimulates granulopoiesis in a congenital neutropenia patient with loss-of-function biallelic heterozygous CSF3R mutations.

Digenic mutations in severe congenital neutropenia.

Severe congenital neutropenia a clinically and genetically heterogeneous disorder. Mutations in different genes have been described as causative for severe neutropenia, e.g. ELANE, HAX1 and G6PC3. Although congenital neutropenia is considered to be a group of monogenic disorders, the phenotypic heterogeneity even within the yet defined genetic subtypes points to additional genetic and/or epigen...

Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: Results of a long-term survey.

Point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3R have been implicated in the progression of severe congenital neutropenia (CN) to leukemia. In this study we present data on a total of 218 patients with chronic neutropenia, including 148 patients with CN (23/148 with secondary malignancies). We detected CSF3R nonsense mutations at 17 different nucl...

Severe congenital neutropenia and chronic neutrophilic leukemia: an intriguing molecular connection unveiled by oncogenic mutations in CSF3R.

Acquired mutations in the colony-stimulating factor 3 receptor gene (CSF3R), truncating the cytosolic region of the CSF3R protein, were discovered almost two decades ago in severe congenital neutropenia (SCN) patients receiving CSF3 treatment to alleviate neutropenia. These CSF3Rmutations are thought to drive clonal expansion by overriding CSF3 hypo-responsiveness of hematopoietic stem and prog...