T618I-Mutated Colony Stimulating Factor 3 Receptor in Chronic Neutrophilic Leukemia and Chronic Myelomonocytic Leukemia Patients who Underwent Allogeneic Stem Cell Transplantation

Lee, Sung‐Eun; Jo, Irene; Jang, Woori; Kim, Yonggoo; Han, Kyungja; Kim, Myungshin

doi:10.3343/alm.2015.35.3.376

Cited by 14 publications

(20 citation statements)

References 9 publications

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“…In that data set of WHO‐defined CNL, the median age at diagnosis was 66 years (range: 15 – 86) and 56% were male . With the discovery of CSFR3 mutations in CNL, comes the opportunity for greater accuracy in true CNL diagnosis: we performed s review of the literature from that point on (2013) and identified a total 57 reported cases of CSF3R ‐mutated CNL, the majority (88%) carrying the CSF3R T618I mutation . The median age (range) was 65 years (10–92) and 70% were male.…”

Section: Epidemiology and Demographicsmentioning

confidence: 79%

“… Two separate series of CSF3R ‐mutated WHO‐defined CNL from China, each reporting eight cases, had similar findings; one showing all eight patients to carry the CSF3R T618I mutation, the other reporting seven of eight cases with a CSF3R T618I, 2 of which were also compound mutations with truncation mutations . In reviewing the literature reported to date, we identified a total 57 cases of CSF3R ‐mutated CNL . Eighty‐eight percent (50 of 57 cases) carried the CSF3R T618I mutation, either alone (n = 30) or in conjunction with a truncation mutations in 25% of the cases ( n = 10) …”

Section: Molecular Pathogenesis Of Cnlmentioning

confidence: 99%

“…As such most of the information regarding this procedure remains anecdotal and is derived from single case reports. We identified nine such reported cases, performed at ages 15, 23, 26, 40 ( n = 2), 49 ( n = 2) and 60 ( n = 2) . All but one (aged 60 years) received myeloablative conditioning, most had sibling donors, although three ases received matched unrelated transplants .…”

Section: Molecularly Targeted Therapymentioning

confidence: 99%

“…We identified nine such reported cases, performed at ages 15, 23, 26, 40 ( n = 2), 49 ( n = 2) and 60 ( n = 2) . All but one (aged 60 years) received myeloablative conditioning, most had sibling donors, although three ases received matched unrelated transplants . The procedure was successful in six cases, with ongoing remission at the time of reporting of more than 78, 73, 54, 36, 7 and 1 month post‐transplantation, respectively .…”

Section: Molecularly Targeted Therapymentioning

confidence: 99%

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Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management

Elliott

Tefferi

2018

American J Hematol

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Disease Overview and Diagnosis: Chronic neutrophilic leukemia (CNL) is a potentially aggressive myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of 25 x 10 9 /L of which 80% are neutrophils, with < 10% circulating neutrophil precursors with blasts rarely observed. In addition, there is no dysplasia, nor clinical or molecular criteria for other myeloproliferative neoplasms.Update on Diagnosis: Previously the diagnosis of CNL was often as one of exclusion based on no identifiable cause for physiologic neutrophilia in patients fulfilling the aforementioned criteria. The 2016 WHO classification now recognizes somatic activating mutations of CSF3R (most commonly CSF3RT618I) as diagnostic, allowing for an accurate diagnosis for the majority of suspected cases through molecular testing. These mutations are primary driver mutations, accounting for the characteristic clinical phenotype and potential susceptibility to molecularly targeted therapy.Risk Stratification: Concurrent mutations, common to myeloid neoplasms and their precursor states, most frequently in SETBP1 and ASXL1, are frequent and appear to be of prognostic significance. Although data are evolving on the full genomic profile, the rarity of CNL has delayed complete understanding of its full molecular pathogenesis and individual patient prognosis.

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Section: Epidemiology and Demographicsmentioning

confidence: 79%

Section: Molecular Pathogenesis Of Cnlmentioning

confidence: 99%

Section: Molecularly Targeted Therapymentioning

confidence: 99%

Section: Molecularly Targeted Therapymentioning

confidence: 99%

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Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management

Elliott

Tefferi

2018

American J Hematol

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“…One‐year OS rates were 54.4% in aCML and 40% in CNL, substantiating the role of allo‐HSCT in improving long‐term survival in CNL. The CSF3R mutation may serve as a biomarker for disease relapse when present at baseline and it may be reasonable to monitor minimal residual disease as CSF3R mutant allele burden post‐HSCT . Given the limited efficacy of available therapeutic agents and CNLʼs often rapidly fatal course, it is currently recommended that eligible patients be considered for HSCT, particularly if they display high‐risk features .…”

Section: Managementmentioning

confidence: 99%

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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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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T618I-Mutated Colony Stimulating Factor 3 Receptor in Chronic Neutrophilic Leukemia and Chronic Myelomonocytic Leukemia Patients who Underwent Allogeneic Stem Cell Transplantation

Cited by 14 publications

References 9 publications

Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management

Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management

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

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

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