Chronic neutrophilic leukemia Chronic neutrophilic leukemia (CNL) is a very rare myeloproliferative neoplasm (MPN) disease, for which there is a lack of sufficient uniform understanding and effective therapeutic measures, therefore, its prognosis is not optimistic. The epidemiology of CNL This disease is very rare and was first reported in 1920 by Tuohy E. Since then, it has been controversial until 2001 when WHO confirmed the diagnostic staging and classified it as a myeloproliferative disease (neoplasm). The WHO revised the diagnostic staging criteria in 2008, and only about 40 cases of CNL were actually diagnosed according to the newly revised criteria [1, 2], indicating that the disease is very rare and thus lacks systematic bulk epidemiological studies. From the analysis of case reports, the disease has a high incidence in the elderly, with a median age of onset of about 66.5 years (15-86 years) and slightly more males than females (about 1:0.7), the disease has a poor prognosis and a short survival, with a median survival of only 23.5 months (1-106 months) and a median time to transformation to acute myeloid leukemia of 21 months (3-94 months), and the most common causes of death are intracranial hemorrhage, disease progression/primary cell transformation, and toxicities associated with chemotherapy or transplantation [1, 3, 4]. The third edition of our Diagnostic and Efficacy Criteria for Hematologic Diseases in 2007 did not include this disease, which also indicates the inconsistency in the understanding of this disease in the academic community.2. Diagnostic criteria for CNL In 2008, WHO proposed the diagnostic criteria for CNL: ① peripheral blood leukocytes ≥ 25X109/L, neutrophil granulocytes and rod-shaped nuclei > 80%, naive cells (including early, middle and late granulocytes) < 10%< span="">, primitive granulocytes <1%< span="">; ② bone marrow aspiration biopsy with significantly increased cell count, increased number and percentage of neutrophils, bone marrow nucleated cell count primitive granulocytes <5%< span="">, normal morphology of mature neutrophils, no pathological hematopoiesis of neutrophils, no monocytes, increased eosinophils; megakaryocytes normal or left shift, may have small hypofractionated megakaryocytes; no significant hyperplasia of reticulofibrillar tissue; (3) hepatosplenomegaly; (4) no cause of physiological neutrophilia, if present, requires cytogenetic or molecular biological evidence of myeloid clones; no infection or inflammatory process; no underlying tumor; (5) no Ph chromosome or BCR/ABL1 fusion gene; (6) no PDGFRA, PDGFRB, or FGFR1 (7) no true erythrocytosis, idiopathic thrombocytosis, or primary osteochondrogenic fibrosis; (8) no evidence of MDS, MPN, and/or MDS/MPN, no abnormal granulocyte development, no MDS changes in other myeloid cells, and monocytes <1x109/L [2,,5. Among the criteria listed, all are basically exclusionary criteria except for criteria ①, ②, and ③. Bone marrow aspiration biopsy is also not the gold standard. Regarding the differential diagnosis of this disease, the main thing is to differentiate it from aCML and CMML [1].3. Cytogenetic examination of CNL Most patients with CNL have normal cytogenetic examination. in a study by Elliott et al [1,,6], about 23% of patients had cytogenetic abnormalities. Common cytogenetic alterations include del(20q), +21, +8,+9, del(11q) and del(12p) [2, 6, 7, 8, 9]. These cytogenetic abnormalities are not specific for determining the diagnosis.4. Molecular biology of CNL The diagnosis of CNL by WHO in previous molecular biology examinations is mainly to exclude other malignant hematological neoplastic diseases [5, 10], such as CML (BCR/ABL1), genetic alterations associated with eosinophilia and other abnormal myeloid and lymphoid system tumors (PDGFRA, PDGFRB or FGFR1) are negative. However, recent advances in molecular biology studies have provided highly valuable tools for the diagnosis of CNL.4.1, JAK2V617F mutation JAK tyrosine kinase plays an extremely important role in cytokine-mediated signaling channels in hematopoietic cells, where erythropoietin, thrombopoietin, and clone-stimulated factor 3 (CSF3), which lacks phosphorylation activity cytokine receptors induce phosphorylation of JAKs by binding to their ligands and further downregulate transcriptional processes such as STAT channels [11]. The JAK2V617F mutation in somatic cells is the most prevalent mutation in classical BCR/ABL1 mutation-negative MPNs, with 95% in PV, 55% in ET, 65% in PMF, less than 20% in non-classical MPNs, 8% in CMML, and rare in MDS and AML [2, 12, 13, 14]. In CNL patients, JAK2V617F mutations are about 5%-20% [4, 15, 16], and the specificity is also poor [17], these findings suggest that JAK2V617F mutations are of very limited value for the diagnosis of CNL.