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2.
Pediatr Transplant ; 22(5): e13199, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29676020

RESUMO

CNL is a rare myeloproliferative disorder frequently seen in older adults. A significant proportion of patients show progression to AML. Here, we report the case of a patient with FA who was monitored for leukopenia but who developed leukocytosis during the follow-up and was diagnosed with CNL probably after an acquired CSF3R mutation. Because the patient had FA, which could accelerate the progression to AML, an HSCT was performed, which resulted in cure. This patient (aged 12 years) is one of the youngest patients reported to develop CNL as well as the first FA patient with a diagnosis of CNL.


Assuntos
Anemia de Fanconi/complicações , Transplante de Células-Tronco Hematopoéticas , Leucemia Neutrofílica Crônica/terapia , Criança , Humanos , Leucemia Neutrofílica Crônica/complicações , Leucemia Neutrofílica Crônica/diagnóstico , Masculino
3.
Blood Cancer J ; 8(2): 19, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29440636

RESUMO

Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent splenomegaly. The seminal discovery of oncogenic driver mutations in CSF3R in the majority of patients with CNL in 2013 generated a new scientific framework for this disease as it deepened our understanding of its molecular pathogenesis, provided a biomarker for diagnosis, and rationalized management using novel targeted therapies. Consequently, in 2016, the World Health Organization (WHO) revised the diagnostic criteria for CNL to reflect such changes in its genomic landscape, now including the presence of disease-defining activating CSF3R mutations as a key diagnostic component of CNL. In this communication, we provide a background on the history of CNL, its clinical and hemopathologic features, and its molecular anatomy, including relevant additional genetic lesions and their significance. We also outline the recently updated WHO diagnostic criteria for CNL. Further, the natural history of the disease is reviewed as well as potential prognostic variables. Finally, we summarize and discuss current treatment options as well as prospective novel therapeutic targets in hopes that they will yield meaningful improvements in patient management and outcomes.


Assuntos
Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/genética , Leucemia Neutrofílica Crônica/terapia , Humanos , Leucemia Neutrofílica Crônica/classificação , Organização Mundial da Saúde
5.
Curr Hematol Malig Rep ; 12(5): 432-441, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28983816

RESUMO

PURPOSE OF REVIEW: We reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients. RECENT FINDINGS: Recent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support considering CSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases. Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy.


Assuntos
Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Leucemia Neutrofílica Crônica , Mutação de Sentido Incorreto , Receptores de Fator Estimulador de Colônias/genética , Substituição de Aminoácidos , Intervalo Livre de Doença , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/mortalidade , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/genética , Leucemia Neutrofílica Crônica/mortalidade , Leucemia Neutrofílica Crônica/terapia , Taxa de Sobrevida
6.
Zhonghua Xue Ye Xue Za Zhi ; 37(8): 688-91, 2016 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-27587251

RESUMO

OBJECTIVE: To explored the diagnosis and treatment of chronic neutrophilic leukemia (CNL) complicated with multiple myeloma (MM). METHODS: The clinical features and molecular biological characteristics of 2 patients with CNL complicated with MM were summarized, and the diagnosis and treatment of the patients were retrospectively reviewed. RESULTS: The diagnosis of CNL complicated with MM was established in 2 cases. Case 1 had CSF3R mutation (P733T), but CSF3R-exon 14 mutation and SETBP1 mutation were all negative. The neutrophil count returned to normal when MM was successfully treated in case 1. When the patient relapsed, neutrophil count increased again. CONCLUSION: Coexistence of CNL and MM is rare. CSF3R is a very important molecular marker for CNL. To the best of our knowledge, it's the first time to report the coexistence of CNL and MM carried CSF3R mutation (P733T). Chemotherapy regimens for MM may be effective in the treatment of CNL complicated with MM.


Assuntos
Leucemia Neutrofílica Crônica/complicações , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/terapia , Mieloma Múltiplo/complicações , Biomarcadores , Proteínas de Transporte , Éxons , Humanos , Mutação , Proteínas Nucleares , Receptores de Fator Estimulador de Colônias , Transdução de Sinais
8.
Curr Opin Hematol ; 22(2): 171-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25575036

RESUMO

PURPOSE OF REVIEW: Chronic neutrophilic leukemia (CNL) is a rare BCR-ABL1-negative myeloid malignancy that is characterized by mature granulocytosis without dysgranulopoiesis. Differential diagnosis of CNL includes reactive or secondary granulocytosis and other myeloid neoplasms, such as atypical chronic myeloid leukemia (aCML) and chronic myelomonocytic leukemia (CMML). Herein, we focus on recently described mutations in CNL and their impact on diagnosis, prognosis and treatment. RECENT FINDINGS: In 2013, membrane-proximal CSF3R mutations, most frequently CSF3RT618I, were described in CNL and aCML. Subsequent studies confirmed the presence of such mutations in nearly all patients with CNL but not in aCML. Furthermore, the majority of the patients with CSF3R-mutated CNL also expressed other mutations, such as SETBP1 and ASXL1, which might be prognostically detrimental. Laboratory studies revealed that CSF3RT618I induced JAK inhibitor-sensitive activation of JAK-STAT and CNL-like disease in mice. Case reports have indicated palliative but not disease-modifying activity of JAK inhibitor therapy in CSF3R-mutated CNL. SUMMARY: CNL is now a morphologically and molecularly defined myeloid malignancy, and no longer a diagnosis of exclusion. The identification of CNL-specific molecular markers provides a much needed pathogenetic insight and also offers the opportunity to revise current diagnostic criteria and identify prognostic biomarkers and potential drug targets.


Assuntos
Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/terapia , Gerenciamento Clínico , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Neutrofílica Crônica/genética , Leucemia Neutrofílica Crônica/mortalidade , Mutação , Neutropenia/congênito , Neutropenia/genética , Prognóstico , Receptores de Fator Estimulador de Colônias/genética
9.
Am J Hematol ; 89(6): 651-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24845374

RESUMO

DISEASE OVERVIEW: Chronic neutrophilic leukemia (CNL) is a myeloproliferative neoplasm characterized by sustained, mature neutrophilic leukocytosis, splenomegaly, and bone marrow granulocytic hyperplasia. DIAGNOSIS: Key diagnostic criteria include leukocytosis of >25 × 10(9) /l (of which >80% are neutrophils) with <10% and <1% circulating immature granulocytes and myeloblasts, respectively. There should be no dysplasia, monocytosis, molecular evidence of BCR-ABL1, PDGFRA, PDGFRB, or FGRF1 rearrangements and no identifiable cause for physiologic neutrophilia or, if present, demonstration of myeloid clonality. DEVELOPMENTS IN MOLECULAR GENETICS: Recently, CNL has been shown to be specifically driven by somatic activating mutations of CSF3R, most commonly CSF3R T618I. As such, the diagnosis of CNL will no longer be one of exclusion only, and revision of the current WHO classification is anticipated to include the molecular criterion of mutated CSF3R.


Assuntos
Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/terapia , Animais , Humanos , Leucemia Neutrofílica Crônica/genética , Biologia Molecular , Transdução de Sinais
10.
Curr Opin Hematol ; 21(2): 148-54, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24335708

RESUMO

PURPOSE OF REVIEW: In the current WHO classification of myeloid disorders, chronic neutrophilic leukaemia (CNL) is recognized as a myeloproliferative neoplasm characterized by sustained neutrophilic leukocytosis, hepatosplenomegaly and bone marrow granulocytic hyperplasia without evidence of dysplasia, BCR-ABL1 or rearrangements of PDGFRA, PDGFRB or FGFR1. This diagnosis is contingent upon exclusion of underlying causes of reactive neutrophilia particularly if evidence of myeloid clonality is lacking. The lack of a specific molecular marker has left the diagnosis to be largely one of exclusion. Recently, the molecular landscape shifted with the discovery of specific oncogenic mutations in the colony-stimulating factor 3 receptor gene (CSF3R) in CNL patients. We review the implications for diagnosis, pathogenesis and potential for new therapeutic options. RECENT FINDINGS: In 2013, oncogenic mutations in CSF3R were identified in a majority of patients with CNL and demonstrated that their downstream signalling was sensitive to known kinase inhibitors. This discovery was then validated with the demonstration of 100% CSF3R mutational frequency (predominately CSF3RT618I) in strictly WHO-defined CNL. Simultaneously, novel somatic mutations in SETBP1 were found to be enriched in CNL with possible prognostic significance. SUMMARY: CNL appears to be driven by specific somatic activating CSF3R mutations. These bestow susceptibility to known kinase inhibitors, opening the door to novel specific therapeutic options for CNL. The diagnosis of CNL will no longer be one only of exclusion, and revision of the current WHO diagnostic criteria is expected to include the molecular criterion of CSF3R mutation positivity.


Assuntos
Leucemia Neutrofílica Crônica/genética , Cromossomos , Progressão da Doença , Humanos , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/epidemiologia , Leucemia Neutrofílica Crônica/terapia , Mutação
11.
Blood ; 122(10): 1707-11, 2013 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-23896413

RESUMO

Although activation of tyrosine kinase pathways is a shared theme among myeloproliferative neoplasms, the pathogenetic basis of chronic neutrophilic leukemia (CNL) has remained elusive. Recently, we identified high-frequency oncogenic mutations in the granulocyte-colony stimulating factor receptor (CSF3R) in CNL and in some patients with atypical chronic myeloid leukemia. Inhibition of Janus kinase 2 or SRC kinase signaling downstream of mutated CSF3R is feasible and should be explored therapeutically. Herein, we discuss the potential impact of these findings for the classification and treatment of these disorders.


Assuntos
Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/genética , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Leucemia Neutrofílica Crônica/patologia , Leucemia Neutrofílica Crônica/terapia , Mutação/genética , Proteínas Nucleares/genética , Receptores de Fator Estimulador de Colônias de Granulócitos/genética
12.
Obstet Gynecol ; 121(2 Pt 2 Suppl 1): 457-60, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23344408

RESUMO

BACKGROUND: Chronic neutrophilic leukemia is a rare myeloproliferative disorder in women of reproductive age. CASE: A pregnant woman with an established diagnosis of chronic neutrophilic leukemia presented at 26 weeks of gestation with splenomegaly, thrombocytopenia, leukocytosis, and anemia. Thrombocytopenia was refractory to medical treatment and, in part, was attributed to splenic sequestration. She delivered a healthy neonate at 35 weeks of gestation by repeat cesarean delivery under general anesthesia. Her preoperative platelet count was 30,000/mL and she was transfused platelets throughout the perioperative period. Her postpartum course was complicated by intraabdominal hemorrhage and severe preeclampsia. She recovered with intensive medical and surgical management. CONCLUSION: Chronic neutrophilic leukemia poses difficult challenges during pregnancy and requires a multidisciplinary approach.


Assuntos
Leucemia Neutrofílica Crônica/terapia , Complicações Neoplásicas na Gravidez/terapia , Cavidade Abdominal/cirurgia , Adulto , Anemia/etiologia , Antineoplásicos/uso terapêutico , Recesariana , Transfusão de Eritrócitos , Feminino , Humanos , Recém-Nascido , Leucemia Neutrofílica Crônica/complicações , Leucocitose/etiologia , Transfusão de Plaquetas , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/cirurgia , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Esplenomegalia/etiologia , Trombocitopenia/etiologia
13.
Pol Arch Med Wewn ; 118(12): 756-60, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19202955

RESUMO

Myeloproliferative syndromes (MPS) are clonal proliferation of hematopoietic progenitor cells characterized by proliferation of 1 or a few cell lines such as granulocytic, erythroid, megakaryocytic or mastocytic. These syndromes include: chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic eosinophilic leukemia/hypereosinophilic syndrome, chronic neutrophilic leukemia and systemic mastocytosis. Diagnosis of MPS is often difficult due to need of differential diagnosis with reactive proliferation caused by primarily non-hematological factors. Differentiation of individual MPS forms is also difficult because of overlapping of particular clinical or laboratory adnormalities. Discovery of specific molecular aberrations in the last few years facilitates diagnostic procedures. The discovered gene mutations or their fusions are associated with production of proteins possessing tyrosine kinase properties. These discoveries resulted in the successful introduction of the targeted therapy with tyrosine kinase inhibitors in the recent years.


Assuntos
Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/terapia , Medula Óssea , Diagnóstico Diferencial , Humanos , Leucemia Eritroblástica Aguda/diagnóstico , Leucemia Eritroblástica Aguda/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/terapia , Transtornos Mieloproliferativos/classificação , Transtornos Mieloproliferativos/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/terapia , Fatores de Risco , Trombocitose/diagnóstico , Trombocitose/terapia
15.
Curr Hematol Rep ; 3(3): 210-7, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15087070

RESUMO

Chronic neutrophilic leukemia (CNL) is recognized as a distinct clinicopathologic entity characterized by sustained mature neutrophilic leukocytosis splenomegaly with bone marrow granulocytic hyperplasia without evidence of dysplasia or striking reticulin fibrosis. This diagnosis is contingent on thorough initial investigation and follow-up to exclude underlying causes of reactive neutrophilia, particularly if evidence of myeloid clonality is lacking. The optimal therapy for CNL remains uncertain. Current management decisions are based on anecdotal reports or extrapolated from therapeutic strategies effective in similar chronic clonal myeloid disorders. Because of the potential for blastic transformation and progressive refractory neutrophilia, allogeneic stem cell transplantation may be appropriate for younger patients. Continued reporting of all cases of CNL and responses to therapeutic strategies must be encouraged.


Assuntos
Leucemia Neutrofílica Crônica/diagnóstico , Medula Óssea/patologia , Células Clonais/patologia , Diagnóstico Diferencial , Humanos , Leucemia Neutrofílica Crônica/patologia , Leucemia Neutrofílica Crônica/terapia , Resultado do Tratamento
16.
Leuk Lymphoma ; 43(10): 2051-4, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12481908

RESUMO

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by a clonal proliferation of mainly mature neutrophils, which is often difficult to differentiate from reactive leukocytosis or other myeloproliferative disorders. Treatment to date has focused on disease control rather than cure. Once the disease has progressed to a more aggressive leukemia there is typically little chance of obtaining a long lasting remission due to the older age of most patients as well as the acquisition of multiple poor prognostic cytogenetic abnormalities. In this case report we describe a successful sibling allogeneic bone marrow transplant in a 60-year-old man with CNL performed while he was still in the stable phase of his disease. We propose that even in older patients this curative approach may be considered in selected patients at an early stage of their disease, similar to the approach taken with chronic myelogenous leukemia.


Assuntos
Transplante de Medula Óssea , Leucemia Neutrofílica Crônica/terapia , Gerenciamento Clínico , Intervalo Livre de Doença , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Leucemia Neutrofílica Crônica/complicações , Leucemia Neutrofílica Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
17.
Cuad. Hosp. Clín ; 47(2): 113-116, 2002. tab
Artigo em Espanhol | LILACS | ID: lil-329741

RESUMO

Se describe un caso de leucemia neutrofílica crónica asociada a leucemia de piel, en una paciente de 49 años de edad, sexo femenino, diagnosticada en julio de 2001; con presencia de 43.605/mm3 neutrófilos en sangre periférica y médula ósea hipercelular con serie granulocítica hiperplástica. el estudio histopatológico de la piel reveló infiltrado del 70 porciento de blastos tipo mieloide. Fue tratada con hidroxiurea, siendo favorable la resuesta clínica y laboratorial. el hemograma de diciembre de 2001 presentó 5.656/mm3 neutrófilos.


Assuntos
Humanos , Adulto , Feminino , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/genética , Leucemia Neutrofílica Crônica/terapia , Leucemia , Pele
18.
Br J Haematol ; 94(4): 628-30, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8826884

RESUMO

Chronic neutrophil leukaemia (CNL) is a rare myeloproliferative disorder predominantly reported in elderly patients. We present a 15-year-old girl and a 25-year-old male with CNL. Clonal cytogenetic abnormalities were detected in both patients. One showed trisomy 21 evolving into tetrasomy 21. The second patient showed a unique chromosome aberration during blast crisis: t(2;2)(q32;p24). Both patients were successfully treated with allogeneic bone marrow transplantation (BMT). CNL should also be considered as a differential diagnosis in adolescence and young adulthood. BMT represents a potentially curative treatment option in such patients.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 21 , Leucemia Neutrofílica Crônica/genética , Adolescente , Adulto , Transplante de Medula Óssea , Feminino , Humanos , Cariotipagem , Leucemia Neutrofílica Crônica/terapia , Masculino , Trissomia
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