Comprehensive Evaluation and Genetic Testing Confirming Chronic Neutrophilic Leukemia: A Case Report from INDIA

Background: Chronic Neutrophilic Leukemia (CNL) is a rare myeloproliferative neoplasm characterized by the proliferation of neutrophilic granulocytes. The most common molecular aberration observed in CNL patients is the somatic activating mutation in colony-stimulatingfactor 3 receptor gene (CSF3R), with the p.Thr618Ile (p.T618I) mutation being predominant and diagnostically crucial. Here, we report a case of CNL, with co-existence of mutations in CSF3RT618I and ASXL1.Case Presentation: We present the case of a 62-year-old male patient with leukocytosis, anemia, and splenomegaly. Laboratory findings showed an elevated white blood cell count with a predominance of neutrophilic segmented cells, a decreased red blood cell count, and reduced hemoglobin levels. Peripheral blood smear and bone marrow examination revealed neutrophilic leukocytosis, myeloid hyperplasia with increased myelocytes, metamyelocytes, and neutrophils,and grade-2 fibrosis. A disease-defining mutation in the colony-stimulating factor 3 receptor gene (CSF3R) was detected, confirming the diagnosis of CNL. Co-occurring mutations in the ASXL1 gene were also identified. Imaging studies confirmed splenomegaly. The absence of the BCR-ABL1 fusion gene commonly associated with chronic myeloid leukemia further supported the diagnosis.Conclusion: This case highlights the importance of comprehensive evaluation, including genetic testing, in confirming the diagnosis of CNL and differentiating it from other hematological disorders. Emerging evidences indicates that mutations in CSF3R (T618I) are early, preleukemic events, while truncation mutations in ASXL1 play a pivotal role in disease progression. This dynamic interplay between genetic alterations sheds light on the disease's pathogenesis, offering insights into potential therapeutic strategies and diagnostic criteria.