Familial occurrence of chronic neutrophilic leukaemia

Kojima, Kensuke; Yasukawa, Masaki; Hara, Masamichi; Nawa, Yuichiro; Kimura, Y; Narumi, Hiroshi; Fujita, Shigeru

doi:10.1046/j.1365-2141.1999.01348.x

Cited by 4 publications

(5 citation statements)

References 11 publications

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“…To date there is a single report in the literature of a familial case of suspected CNL involving a father and son who both developed the disease 33 . The father had previously been exposed to radiation following the atomic bomb attack on Hiroshima however, and the oncogenetic effect of this remains a potentially confounding pathogenic factor.…”

Section: Genetic Predispositionmentioning

confidence: 99%

Chronic neutrophilic leukemia: new science and new diagnostic criteria

Szuber

Tefferi

2018

Blood Cancer Journal

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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.

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Section: Genetic Predispositionmentioning

confidence: 99%

Chronic neutrophilic leukemia: new science and new diagnostic criteria

Szuber

Tefferi

2018

Blood Cancer Journal

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“…For blast phase, standard induction chemotherapy was successful at attaining a second chronic phase in one patient only . In the remaining patients, the leukemia was either refractory, the marrow remained hypoplastic following induction chemotherapy, or death occurred during attempts at remission induction . A similar situation has been observed among patients with refractory progressive neutrophilia .…”

Section: Managementmentioning

confidence: 72%

“…At that time, only ∼150 cases had been reported in the literature . A critical review of the literature applying the then recently developed WHO diagnostic criteria, could only confirm this diagnosis in forty cases, indicating a lower rate of occurrence of what is now considered CNL . In the combined data set of WHO‐defined cases, the median age at diagnosis was 66 years (range: 15–86) and 56% were male .…”

Section: Disease Overview and Diagnosismentioning

confidence: 99%

Chronic neutrophilic leukemia 2014: Update on diagnosis, molecular genetics, and management

Elliott

Tefferi

2014

American J Hematol

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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 × 109/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. Am. J. Hematol. 89:651–658, 2014. © 2014 Wiley Periodicals, Inc.

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“…Although the true prevalence of constitutional CNL is undefined, there are currently three suspected familial cases of CNL reported 26,27 ; only the most recently described one, however, represents inherited transmission of CSF3RT618I confirmed through targeted high throughput sequencing of germline DNA. 28 Germline CSF3R status should therefore be assessed in suspected familial cases.…”

Section: Genetic Predispositionmentioning

confidence: 99%

Chronic neutrophilic leukemia: 2022 update on diagnosis, genomic landscape, prognosis, and management

2022

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Disease Overview: Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) defined by persistent mature neutrophilic leukocytosis, bone marrow granulocyte hyperplasia, and frequent hepatosplenomegaly.The 2013 seminal discovery of oncogenic driver mutations in colony-stimulating factor 3 receptor (CSF3R) in the majority of patients with CNL not only established its molecular pathogenesis but provided a diagnostic biomarker and rationale for pharmacological targeting.Diagnosis: In 2016, the World Health Organization (WHO) recognized activating CSF3R mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of ≥25 Â 10 9 /L comprising >80% neutrophils with <10% circulating precursors and rare blasts, and absence of dysplasia or monocytosis, while not fulfilling criteria for other MPN.Management: There is currently no standard of care for management of CNL, due in large part to the rarity of disease and dearth of formal clinical trials. Most commonly used therapeutic agents include conventional oral chemotherapy (e.g., hydroxyurea), interferon, and Janus kinase (JAK) inhibitors, while hematopoietic stem cell transplant remains the only potentially curative modality.Disease Updates: Increasingly comprehensive genetic profiling in CNL, including new data on clonal evolution, has disclosed a complex genomic landscape with additional mutations and combinations thereof driving disease progression and drug resistance.Although accurate prognostic stratification and therapeutic decision-making remain challenging in CNL, emerging data on molecular biomarkers and the addition of newer agents, such as JAK inhibitors, to the therapeutic arsenal, are paving the way toward greater standardization and improvement of patient care.

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Familial occurrence of chronic neutrophilic leukaemia

Cited by 4 publications

References 11 publications

Chronic neutrophilic leukemia: new science and new diagnostic criteria

Chronic neutrophilic leukemia: new science and new diagnostic criteria

Chronic neutrophilic leukemia 2014: Update on diagnosis, molecular genetics, and management

Chronic neutrophilic leukemia: 2022 update on diagnosis, genomic landscape, prognosis, and management

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