# Colony-Stimulating Factor 3 Receptor Mutations and Variants in Hematological Malignancies

## TL;DR

This paper reviews mutations in the CSF3R gene and their roles in various blood and immune cell cancers.

## Contribution

The paper provides a comprehensive overview of CSF3R mutations and their clinical and biological impacts in hematological malignancies.

## Key findings

- CSF3R mutations are linked to chronic neutrophilic leukemia and other myeloproliferative neoplasms.
- Variants in CSF3R contribute to myelodysplastic neoplasms and acute myeloid leukemia.
- CSF3R mutations also affect lymphoid malignancies and combined myeloid disorders.

## Abstract

Cells can communicate via the release of small proteins that bind to specific receptors on the surface of other cells, with so-called ‘cytokine receptors’ particularly important for blood and immune cells. One such cytokine receptor, named ‘colony-stimulating factor 3 receptor’ (or ‘CSF3R’), regulates the production and function of a group of white blood cells called neutrophils. Mutations and variants in the gene that produces CSF3R have been identified in blood and immune cell cancers. Here, we review the different CSF3R forms and their role in specific diseases.

Colony-stimulating factor 3 (CSF3), additionally called granulocyte colony-stimulating factor (G-CSF), is the major cytokine regulating neutrophil production and also impacting their function. The actions of this cytokine are mediated through its unique receptor, the colony-stimulating factor 3 receptor (CSF3R). Several classes of pathogenic mutations in the CSF3R gene have been identified that have distinct biological properties and clinical impacts. This review provides an overview of CSF3R, the various pathogenic CSF3R mutations/variants and their biological effects. It also details the diseases to which they contribute, notably including chronic neutrophilic leukemia (CNL) and other myeloproliferative neoplasms (MPNs), myelodysplastic neoplasms (MDS), combined MDS/MPN disorders such as atypical chronic myeloid leukemia (aCML) and chronic myelomonocytic leukemia (CMML), as well as acute myeloid leukemia (AML) and lymphoid malignancies.