Csf3r, also known as the receptor for colony-stimulating factor 3, is a key component in the granulocyte colony-stimulating factor (G-CSF) signalling pathway. It plays a crucial role in the maturation of neutrophil granulocytes. The G-CSF signalling pathway, in which Csf3r is involved, is essential for haematopoietic processes, especially those related to the production and regulation of neutrophils [3].

Activating mutations in Csf3r are frequently observed in chronic neutrophilic leukemia (CNL) and a subset of atypical chronic myeloid leukemia (aCML). In fact, these mutations were identified in 59% of patients with CNL or aCML, and they lead to preferential downstream kinase signalling through SRC family-TNK2 or JAK kinases, along with differential sensitivity to kinase inhibitors [1]. Additionally, Csf3r mutations are not restricted to CNL. They can also occur in other myeloid neoplasms such as acute myeloid leukemia (AML), chronic myelomonocytic leukemia, and myeloproliferative neoplasm. Co-occurring mutations are often in epigenetic modifier and spliceosome genes, and specific mutations like IDH/RUNX1 and tumor suppressor mutations are frequent in AML but absent in CNL/aCML [2].

In conclusion, Csf3r is vital for neutrophil granulocyte maturation through its role in the G-CSF signalling pathway. The discovery of its activating mutations in CNL, aCML, and other myeloid neoplasms has significant implications for understanding the pathogenesis of these diseases. The study of Csf3r in these contexts helps in identifying potential diagnostic criteria and targeted therapeutic strategies for related haematological malignancies.

References:

1. Maxson, Julia E, Gotlib, Jason, Pollyea, Daniel A, Druker, Brian J, Tyner, Jeffrey W. . Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. In The New England journal of medicine, 368, 1781-90. doi:10.1056/NEJMoa1214514. https://pubmed.ncbi.nlm.nih.gov/23656643/

2. Mohamed, Ahmed, Gao, Juehua, Chen, Yi-Hua, Lu, Xinyan, Chen, Qing. 2024. CSF3R mutated myeloid neoplasms: Beyond chronic neutrophilic leukemia. In Human pathology, 149, 66-74. doi:10.1016/j.humpath.2024.06.008. https://pubmed.ncbi.nlm.nih.gov/38879086/

3. Skokowa, Julia, Dale, David C, Touw, Ivo P, Zeidler, Cornelia, Welte, Karl. 2017. Severe congenital neutropenias. In Nature reviews. Disease primers, 3, 17032. doi:10.1038/nrdp.2017.32. https://pubmed.ncbi.nlm.nih.gov/28593997/