Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology

Abstract

Hematological malignancies often develop due to a vast spectrum of environmental and genetic etiologies. Chronic neutrophilic leukemia (CNL) can be described as a BCR-ABL1 (Philadelphia chromosome)-negative myeloproliferative neoplastic disease with various genetic mutations that may directly or indirectly play a role in its pathogenesis. A well-established mutation in CNL is the CSF3R (a cytokine receptor) which has been incorporated into the diagnostic criteria for the disease. However, evidence of other mutations such as SETBP1, ASXL1, and TET2 has also shed more light on the pathogenesis of this condition. Due to the unknown incidence and heterogeneous presentation of the disease, the diagnosis and management are often difficult and lack satisfactory data. The purpose of this review is to yield further insight into a disease that lacks awareness in the medical community. Using PubMed as a database, relevant studies and case reports were reviewed. The data compiled were used to acknowledge the disease in terms of etiology, clinical manifestation, molecular pathogenesis, and available treatment modalities. Though existing treatment modalities have been shown to induce clinical improvement, the outcomes are not reliable, and further research is required to reach a comprehensive "standard of care" for the disease.

The impact of SETBP1 mutations in neurological diseases and cancer

“…Patients with colony‐stimulating factor 3 receptor ( CSFR3 ) mutations, which account for more than half of the CNL patients, have a high frequency of SETBP1 mutations. The concomitant occurrence of these mutations exacerbates CNL by upregulating the expression of c‐Myc and its target genes (Anil et al, 2021; Carratt et al, 2022; Qian et al, 2021). Approximately, 85% of juvenile myelomonocytic leukemia (JMML) patients have JAK3 mutations.…”