BACKGROUNDChronic neutrophilic leukemia (CNL) is a rare bone marrow proliferative tumorand a heterogeneous disorder. In 2016, the World Health Organization includedactivating mutations in the CSF3R gene as one of the ...BACKGROUNDChronic neutrophilic leukemia (CNL) is a rare bone marrow proliferative tumorand a heterogeneous disorder. In 2016, the World Health Organization includedactivating mutations in the CSF3R gene as one of the diagnostic criteria, withCSF3R T618I being the most common mutation. The disease is often accompaniedby splenomegaly, but no developmental abnormalities and significant reticularfibrosis, and no Ph chromosome and BCR-ABL fusion gene. So, it is difficult todiagnose at the first presentation in the absence of classical symptoms. Herein wedescribe a rare CNL patient without splenomegaly whose initial diagnostic cluewas neutrophilic hyperactivity.CASE SUMMARYThe patient is an 80-year-old Han Chinese man who presented with one month offatigue and fatigue aggravation in the last half of the month. He had nosplenomegaly, but had persistent hypofibrinogenemia, obvious skin bleeding, andhemoptysis, and required repeated infusion of fibrinogen therapy. After manyrelevant laboratory examinations, histopathological examination, and sequencinganalysis, the patient was finally diagnosed with CNL [CSF3R T618I positive:c.1853C>T (p.T618I) and c.2514T>A (p.C838)].CONCLUSIONThe physical examination and blood test for tumor-related genes are insufficientto establish a diagnosis of CNL. Splenomegaly is not that important, buthyperplasia of interstitial neutrophil system and activating mutations in CSF3Rare important clues to CNL diagnosis.展开更多
Objective To review the implications for diagnosis, pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia （CNL）. Data sources Data cited in this review were obtained mainly from Pub...Objective To review the implications for diagnosis, pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia （CNL）. Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1993 to 2013 and highly regarded older publications were also included. The terms ＂chronic neutrophilic leukemia＂ and ＂diagnosis＂ were used for the literature search. Study selection We identified, retrieved and reviewed the information on the clinical and laboratory features, the new genetic findings, prognosis and disease evolution and management of CNL. Results The discovery of high-frequency granulocyte-colony stimulating factor receptor （CSF3R） mutations in CNL identifies a new major diagnostic criterion, and lends more specificity to the World Health Organization （WHO） diagnostic criteria for CNL, which are variably applied in routine clinical practice. Conclusions In patients for whom the cause of neutrophilia is not easily discerned, the incorporation of CSF3R mutation testing can be a useful point-of-care diagnostic to evaluate the presence of a clonal myeloid disorder, as well as providing the potential for genetically informed therapy. The oncogenic CSF3R mutations are molecular markers of sensitivity to inhibitors of the SRC family-TNK2 and JAK kinases and may provide a new avenue for therapy.展开更多
文摘BACKGROUNDChronic neutrophilic leukemia (CNL) is a rare bone marrow proliferative tumorand a heterogeneous disorder. In 2016, the World Health Organization includedactivating mutations in the CSF3R gene as one of the diagnostic criteria, withCSF3R T618I being the most common mutation. The disease is often accompaniedby splenomegaly, but no developmental abnormalities and significant reticularfibrosis, and no Ph chromosome and BCR-ABL fusion gene. So, it is difficult todiagnose at the first presentation in the absence of classical symptoms. Herein wedescribe a rare CNL patient without splenomegaly whose initial diagnostic cluewas neutrophilic hyperactivity.CASE SUMMARYThe patient is an 80-year-old Han Chinese man who presented with one month offatigue and fatigue aggravation in the last half of the month. He had nosplenomegaly, but had persistent hypofibrinogenemia, obvious skin bleeding, andhemoptysis, and required repeated infusion of fibrinogen therapy. After manyrelevant laboratory examinations, histopathological examination, and sequencinganalysis, the patient was finally diagnosed with CNL [CSF3R T618I positive:c.1853C>T (p.T618I) and c.2514T>A (p.C838)].CONCLUSIONThe physical examination and blood test for tumor-related genes are insufficientto establish a diagnosis of CNL. Splenomegaly is not that important, buthyperplasia of interstitial neutrophil system and activating mutations in CSF3Rare important clues to CNL diagnosis.
文摘Objective To review the implications for diagnosis, pathogenesis and potential for new therapeutic option for chronic neutrophilic leukemia （CNL）. Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1993 to 2013 and highly regarded older publications were also included. The terms ＂chronic neutrophilic leukemia＂ and ＂diagnosis＂ were used for the literature search. Study selection We identified, retrieved and reviewed the information on the clinical and laboratory features, the new genetic findings, prognosis and disease evolution and management of CNL. Results The discovery of high-frequency granulocyte-colony stimulating factor receptor （CSF3R） mutations in CNL identifies a new major diagnostic criterion, and lends more specificity to the World Health Organization （WHO） diagnostic criteria for CNL, which are variably applied in routine clinical practice. Conclusions In patients for whom the cause of neutrophilia is not easily discerned, the incorporation of CSF3R mutation testing can be a useful point-of-care diagnostic to evaluate the presence of a clonal myeloid disorder, as well as providing the potential for genetically informed therapy. The oncogenic CSF3R mutations are molecular markers of sensitivity to inhibitors of the SRC family-TNK2 and JAK kinases and may provide a new avenue for therapy.
