G-CSF receptor mutations in patients with congenital neutropenia

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Purpose of review

In this review, we summarize our current knowledge on the acquisition of granulocyte-colony stimulating factor receptor (G-CSFR) gene (CSF3R) mutations in patients with congenital neutropenia and their role in leukemogenesis. Congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 × 109/l.

Recent findings

There are two major subtypes of congenital neutropenia as judged by inheritance, comprising the majority of congenital neutropenia patients: autosomal dominant trait defined by neutrophil elastase mutations consisting of 60% of patients and autosomal recessive trait comprising approximately 30% of patients, both presenting with the same clinical and morphological phenotype. Congenital neutropenia is considered as a preleukemic syndrome, as the cumulative incidence for leukemia is more than 25% after 20 years of observation. Acquired CSF3R mutations are detected in approximately 80% of congenital neutropenia patients who developed acute myeloid leukemia suggesting that these mutations are involved in leukemogenesis. One possible pathomechanism causing leukemia is that clones of cells harboring acquired CSF3R mutations have a growth advantage over wild type cells in vivo during granulocyte-colony stimulating factor treatment due to activation of STAT5 and ß-catenin, both known to be involved in leukemogenesis.


Congenital neutropenia patients with acquired CSF3R mutations define a group with high risk for development of leukemia.

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