Chronic neutrophilic leukaemia

Uppal, Guldeep; Gong, Jerald Z.

doi:10.1136/jclinpath-2015-203060

Cited by 12 publications

(11 citation statements)

References 45 publications

(76 reference statements)

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“…A disproportionately high number of cases of CNL associated with plasma cell neoplasms have been reported considering the rarity of this disease, even prompting the distinction of a “monoclonal gammopathy‐associated CNL” or MG‐CNL entity. Plasma cell dyscrasias have been shown to occur in up to 32% of CNL cases . In a recent review on this subject, after excluding suspected cases of CNL not meeting WHO criteria, ultimately, 49 patients with “CNL” or neutrophilic leukemoid reaction associated with multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) were identified in the literature .…”

Section: Disease Features and Diagnosissupporting

confidence: 60%

Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management

2019

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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 seminal discovery of oncogenic driver mutations in colony-stimulating factor 3 receptor (CSF3R) in the majority of patients with CNL in 2013 anchored a new scientific framework, deepening our understanding of its molecular pathogenesis, providing a diagnostic biomarker, and rationalizing the use of pharmacological targeting. Diagnostic criteria: In 2016, the World Health Organization (WHO) included the presence of activating CSF3R mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of ≥25 × 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.Disease updates: Increasingly comprehensive genetic profiling of CNL has disclosed a complex genomic landscape and additional prognostically relevant mutational combinations. Though prognostic determination and therapeutic decision-making remain challenging, emerging data on prognostic markers and the use of newer therapeutic agents, such as JAK inhibitors, are helping to define state-of-the-art management in CNL.

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Section: Disease Features and Diagnosissupporting

confidence: 60%

Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management

2019

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“…As discussed previously, T618I is an auto-activating transmembrane proximal CSF3R mutation (28, 64–68). In one report, the auto-activation of the receptor was thought to be caused by the loss of an O-glycosylation site on T618I (69).…”

Section: Chronic Neutrophilic Leukemia (Cnl) and Mutations In Csf3rmentioning

confidence: 88%

“…CNL is a rare but fatal disease with pathological features of refractory neutrophilia, worsening organomegaly and blastic transformation (64). Maxson et al 2013 first described the connection between CSF3R mutation and CNL (41).…”

Section: Chronic Neutrophilic Leukemia (Cnl) and Mutations In Csf3rmentioning

confidence: 99%

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Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies

Dwivedi

Greis

2017

Experimental Hematology

120

111

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Granulocyte colony stimulating factor (G-CSF) is a hematopoietic cytokine that stimulates neutrophil production and hematopoietic stem cell mobilization by initiating the dimerization of homodimeric granulocyte colony stimulating factor receptor (G-CSFR). Different mutations of CSF3R have been linked to a unique spectrum of myeloid disorders and related malignancies. Myeloid disorders caused by the CSF3R mutations include severe congenital neutropenia (SCN), chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). In this review, we provide an analysis of G-CSFR, various mutations and their roles in the SCN, CNL and malignant transformation as well as the clinical implications and some perspective on approaches that could expand our knowledge with respect to the normal signaling mechanisms and those associated with mutations in the receptor.

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“…A disproportionately high number of cases of CNL associated with plasma cell neoplasms have been reported considering the rarity of this disease 57 – 65 , even prompting the distinction of a “monoclonal gammopathy-associated CNL” or MG-CNL entity. Plasma cell dyscrasias have been shown to occur in up to 32% of CNL cases 66 . In a recent review on this subject, after excluding suspected cases of CNL not meeting WHO criteria, ultimately, 49 patients with “CNL” or neutrophilic leukemoid reaction associated with multiple myeloma or MGUS were found in the literature 13 .…”

Section: Disease Associationsmentioning

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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Chronic neutrophilic leukaemia

Abstract: Chronic neutrophilic leukaemia (CNL) is a rare type of myeloproliferative neoplasm (MPN) characterised by sustained leucocytosis (≥25×10 9

Cited by 12 publications

References 45 publications

Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management

Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management

Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies

Chronic neutrophilic leukemia: new science and new diagnostic criteria

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