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
Colony-stimulating factor 3 receptor(CSF3R)mutations have been identified in a variety of myeloid disorders.Although CSF3R point mutations(eg,T618I)are emerging as key players in chronic neutrophilic leukemia/atypical...Colony-stimulating factor 3 receptor(CSF3R)mutations have been identified in a variety of myeloid disorders.Although CSF3R point mutations(eg,T618I)are emerging as key players in chronic neutrophilic leukemia/atypical chronic myelogenous leukemia,the significance of rarer CSF3R mutations is unknown.Here,we report a 32-year-old female who was diagnosed as Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph^(+)ALL)with the CSF3R M696T mutation and was undergone unrelated donor hematopoietic stem cell transplantation.The patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor(TKI)and long-term survival by unrelated donor transplantation.Meanwhile,we performed a series of experiments using murine interleukin 3(IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation.We confirmed the presence of a CSF3R M696T germline mutation in this patient which was inherited from her mother.The in vitro experiment results showed that the CSF3R M696T mutation contributes marginally to the tumor transformation of Ba/F3 cells,indicating that CSF3R M696T mutation was neutral in tumor transformation ability.We concluded that TKI is effective in patients with the CSF3R M696T mutation in Ph+ALL and donors with CSF3R M696T mutation might still be selected as the candidate for transplantation.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.
基金This work was supported by funds from the Ministry of Science and Technology of China(2018YFA0107801 and 2017YFA0103402)the National Natural Science Foundation of China(82070192,81770105,81770155,and 81670171).
文摘Colony-stimulating factor 3 receptor(CSF3R)mutations have been identified in a variety of myeloid disorders.Although CSF3R point mutations(eg,T618I)are emerging as key players in chronic neutrophilic leukemia/atypical chronic myelogenous leukemia,the significance of rarer CSF3R mutations is unknown.Here,we report a 32-year-old female who was diagnosed as Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph^(+)ALL)with the CSF3R M696T mutation and was undergone unrelated donor hematopoietic stem cell transplantation.The patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor(TKI)and long-term survival by unrelated donor transplantation.Meanwhile,we performed a series of experiments using murine interleukin 3(IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation.We confirmed the presence of a CSF3R M696T germline mutation in this patient which was inherited from her mother.The in vitro experiment results showed that the CSF3R M696T mutation contributes marginally to the tumor transformation of Ba/F3 cells,indicating that CSF3R M696T mutation was neutral in tumor transformation ability.We concluded that TKI is effective in patients with the CSF3R M696T mutation in Ph+ALL and donors with CSF3R M696T mutation might still be selected as the candidate for transplantation.
