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Chronic neutrophilic leukemia: a clinical perspective.

Menezes J, Cigudosa JC - Onco Targets Ther (2015)

Bottom Line: However, this scenario changed with the identification of oncogenic mutations in the CSF3R gene in approximately 83% of WHO-defined and no monoclonal gammopathy-associated CNL patients.In addition to CSF3R mutations, other genetic alterations have been found, notably mutations in SETBP1, which may be used as prognostic markers to guide therapeutic decisions.In this review, we discuss the new genetic alterations recently found in CNL and the clinical perspectives in its diagnosis and treatment.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre - CNIO, Madrid, Spain.

ABSTRACT
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) that includes only 150 patients described to date meeting the latest World Health Organization (WHO) criteria and the recently reported CSF3R mutations. The diagnosis is based on morphological criteria of granulocytic cells and the exclusion of genetic drivers that are known to occur in others MPNs, such as BCR-ABL1, PDGFRA/B, or FGFR1 rearrangements. However, this scenario changed with the identification of oncogenic mutations in the CSF3R gene in approximately 83% of WHO-defined and no monoclonal gammopathy-associated CNL patients. CSF3R T618I is a highly specific molecular marker for CNL that is sensitive to inhibition in vitro and in vivo by currently approved protein kinase inhibitors. In addition to CSF3R mutations, other genetic alterations have been found, notably mutations in SETBP1, which may be used as prognostic markers to guide therapeutic decisions. These findings will help to understand the pathogenesis of CNL and greatly impact the clinical management of this disease. In this review, we discuss the new genetic alterations recently found in CNL and the clinical perspectives in its diagnosis and treatment. Fortunately, since the diagnosis of CNL is not based on exclusion anymore, the molecular characterization of the CSF3R gene must be included in the WHO criteria for CNL diagnosis.

No MeSH data available.


Related in: MedlinePlus

Algorithm for CNL diagnosis and treatment.Notes: The presence of a membrane proximal CSF3R mutation in a patient with predominantly neutrophilic granulocytosis should be sufficient for the diagnosis of CNL.Abbreviations: CNL, chronic neutrophilic leukemia; PB, peripheral blood; JAK2, Janus kinase 2; AML, acute myeloid leukemia.
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f3-ott-8-2383: Algorithm for CNL diagnosis and treatment.Notes: The presence of a membrane proximal CSF3R mutation in a patient with predominantly neutrophilic granulocytosis should be sufficient for the diagnosis of CNL.Abbreviations: CNL, chronic neutrophilic leukemia; PB, peripheral blood; JAK2, Janus kinase 2; AML, acute myeloid leukemia.

Mentions: Very recently, Tefferi et al52 proposed a classification system for ET/PMF and CNL, based on the new genetic findings to be incorporated in the new WHO classification criteria for MPN. Such availability of a clonal marker for the majority of patients with CNL should allow lowering of the leukocyte level to 13×109/L, consistent with that is currently being used for the diagnosis of WHO-defined aCML (Figure 3).5 In addition, the authors proposed separate sets of major and minor criteria to accommodate the diagnostic possibility in both CSF3R-mutated and unmutated CNL. In this algorithm, diagnosis requires the presence of all three major criteria (leukocytosis WBC ≥13×109/L; segmented neutrophils/band >80% and CSF3R mutations) or, in the absence of CSF3R mutations, all minor criteria (hypercellular BM; immature granulocytes <10% in PB; no cause for neutrophilia or, if so, demonstration of clonality; no BCR-ABL1 rearrangements; and no meeting WHO diagnostic criteria for other myeloid neoplasm).


Chronic neutrophilic leukemia: a clinical perspective.

Menezes J, Cigudosa JC - Onco Targets Ther (2015)

Algorithm for CNL diagnosis and treatment.Notes: The presence of a membrane proximal CSF3R mutation in a patient with predominantly neutrophilic granulocytosis should be sufficient for the diagnosis of CNL.Abbreviations: CNL, chronic neutrophilic leukemia; PB, peripheral blood; JAK2, Janus kinase 2; AML, acute myeloid leukemia.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4562747&req=5

f3-ott-8-2383: Algorithm for CNL diagnosis and treatment.Notes: The presence of a membrane proximal CSF3R mutation in a patient with predominantly neutrophilic granulocytosis should be sufficient for the diagnosis of CNL.Abbreviations: CNL, chronic neutrophilic leukemia; PB, peripheral blood; JAK2, Janus kinase 2; AML, acute myeloid leukemia.
Mentions: Very recently, Tefferi et al52 proposed a classification system for ET/PMF and CNL, based on the new genetic findings to be incorporated in the new WHO classification criteria for MPN. Such availability of a clonal marker for the majority of patients with CNL should allow lowering of the leukocyte level to 13×109/L, consistent with that is currently being used for the diagnosis of WHO-defined aCML (Figure 3).5 In addition, the authors proposed separate sets of major and minor criteria to accommodate the diagnostic possibility in both CSF3R-mutated and unmutated CNL. In this algorithm, diagnosis requires the presence of all three major criteria (leukocytosis WBC ≥13×109/L; segmented neutrophils/band >80% and CSF3R mutations) or, in the absence of CSF3R mutations, all minor criteria (hypercellular BM; immature granulocytes <10% in PB; no cause for neutrophilia or, if so, demonstration of clonality; no BCR-ABL1 rearrangements; and no meeting WHO diagnostic criteria for other myeloid neoplasm).

Bottom Line: However, this scenario changed with the identification of oncogenic mutations in the CSF3R gene in approximately 83% of WHO-defined and no monoclonal gammopathy-associated CNL patients.In addition to CSF3R mutations, other genetic alterations have been found, notably mutations in SETBP1, which may be used as prognostic markers to guide therapeutic decisions.In this review, we discuss the new genetic alterations recently found in CNL and the clinical perspectives in its diagnosis and treatment.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre - CNIO, Madrid, Spain.

ABSTRACT
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) that includes only 150 patients described to date meeting the latest World Health Organization (WHO) criteria and the recently reported CSF3R mutations. The diagnosis is based on morphological criteria of granulocytic cells and the exclusion of genetic drivers that are known to occur in others MPNs, such as BCR-ABL1, PDGFRA/B, or FGFR1 rearrangements. However, this scenario changed with the identification of oncogenic mutations in the CSF3R gene in approximately 83% of WHO-defined and no monoclonal gammopathy-associated CNL patients. CSF3R T618I is a highly specific molecular marker for CNL that is sensitive to inhibition in vitro and in vivo by currently approved protein kinase inhibitors. In addition to CSF3R mutations, other genetic alterations have been found, notably mutations in SETBP1, which may be used as prognostic markers to guide therapeutic decisions. These findings will help to understand the pathogenesis of CNL and greatly impact the clinical management of this disease. In this review, we discuss the new genetic alterations recently found in CNL and the clinical perspectives in its diagnosis and treatment. Fortunately, since the diagnosis of CNL is not based on exclusion anymore, the molecular characterization of the CSF3R gene must be included in the WHO criteria for CNL diagnosis.

No MeSH data available.


Related in: MedlinePlus