Chronic Neutrophilic Leukemia

Understanding the dichotomous effects of IFNs in MPNs not only clarifies their role in disease biology but also informs their optimal use in clinical practice. This duality highlights the need for personalized approaches to IFN-based therapies.

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.

In-depth research on the CSF3R genes and their related mechanisms will help further reveal the mechanisms of leukemia development and provide potential targets for treatment. Therefore, this paper mainly focuses on the roles of colony-stimulating factor 3 (CSF3R) in hematopoiesis and the occurrence of leukemia, with particular attention to the roles of CSF3R in the JAK-STAT, PI3K-AKT, and MAPK-ERK signaling pathways.

Survival analysis revealed distinct patterns across the three diagnostic groups, with MDS/MPN having the poorest prognosis. This study expands the recognized spectrum of CSF3R-related myeloid neoplasms and highlights the clinical and molecular heterogeneity associated with these mutations, emphasizing the need for comprehensive molecular profiling and the potential for targeted therapies.

P1, N=18, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P=N/A, N=153, Active, not recruiting, City of Hope Medical Center | Completed --> Active, not recruiting | Trial completion date: Dec 2013 --> Dec 2025

P=N/A, N=153, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P=N/A, N=153, Active, not recruiting, City of Hope Medical Center | Completed --> Active, not recruiting | Trial completion date: Dec 2013 --> Dec 2025

GSEA identified CNL-5-associated pathways, such as the inhibition of oxidative phosphorylation and the activation of IL6-JAK-STAT3 signaling. A novel expression signature-based diagnostic assessment for CNL was developed, which showed better diagnostic utility than conventional indicators.

Similarly, in MDS/MPN with thrombocytosis, transplantation is recommended based on established MDS guidelines. Given the current lack of robust evidence, this document will serve as a valuable resource to guide future research activities, providing a framework for addressing critical unanswered questions and advancing the field.

CMML cases with T618I variant showed a myeloproliferative phenotype. Overall, our findings support the notion that CSF3R variants, particularly type I and II pathogenic mutations, may modulate the phenotypic features of leukemic cells in myeloid neoplasia.