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Objective: To provide clinical basis for the diagnosis and treatment of chronic neutrophilic leukemia (CNL) and to provide possible molecular targets for the treatment.
Methods: By summarizing the clinical data of 14 patients with CNL, the clinical characteristics, gene mutation types and possible prognostic factors were analyzed.
Results: Among the 14 patients with CNL, males (9 cases) were more than females (5 cases), with a median age of 57 years old. The detection rate of CSF3R mutation was 92.86% (13/14), including 12 cases (85.71%) with T318I mutation and 1 case of Y799X mutation, and only 1 case was not detected for mutation of CSF3R. The ASXL1 mutation was detected in 42.86% (6/14) of the patients, all of which were nonsense mutations, including 4 cases with R693X and 2 cases with E705X, and 14.29% (2/14) of the patients was detected for SETBP1 mutation, all of which were with D868N mutation. No patients with simultaneous ASXL1 and SETBP1 mutations were found, and JAK2 and CALR mutations were not detected. All of the patients had normal karyotypes. These patients' median survival time was 30 months (95%CI 13.19-46.80), and the influence of age over 60 years old was statistically significant (21.83 months vs 35.35 months) (P<0.05).
Conclusion: It is difficult to diagnose CNL. CSF3R T618I mutation is its specific mutation, and ASXL1 mutation and SETBP1 mutation have auxiliary diagnostic significance for CNL. The age>60 years old at diagnosis is a factor of unfavourable prognosis.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.01.014 | DOI Listing |
Haematologica
September 2025
Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine/NewYork-Presbyterian Hospital, New York, NY; Multiparametric In Situ Imaging (MISI) Laboratory, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York.
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View Article and Find Full Text PDFHaematologica
September 2025
Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel.
We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a high-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors.
View Article and Find Full Text PDFJ Cell Sci
September 2025
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
The microtubule motor dynein-2 is responsible for retrograde intraflagellar transport (IFT), a process critical for cilia assembly and cilium-dependent signaling. Mutations in genes encoding dynein-2 subunits interfere with ciliogenesis and are among the most frequent causes of skeletal ciliopathies. Despite its importance, little is known regarding dynein-2 assembly and regulation.
View Article and Find Full Text PDFRev Med Liege
September 2025
Service d'Oncologie Médicale, CHU Liège, Belgique.
This review aims to describe the role of poly-ADP-ribose polymerase inhibitors (PARPi) in the treatment of metastatic castration-resistant prostate cancer (mCRPC), an aggressive and lethal form of the disease. The introduction of PARPi has led to improved prognosis, particularly in patients with at least one somatic or germline mutation in DNA damage repair genes such as BRCA1 or BRCA2. Several recent studies have shown that PARPi, used alone or in combination with abiraterone or enzalutamide, improve progression-free survival and overall survival in patients with mCRPC.
View Article and Find Full Text PDFMol Cell Biol
September 2025
Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Mammalian cell membranes contain ether lipids, which include an alkyl chain derived from a fatty alcohol that is produced by fatty acyl-CoA reductases (FARs). There are two mammalian FAR genes, and , and mutations in cause the peroxisomal fatty acyl-CoA reductase 1 disorder (PFCRD), which is accompanied by various symptoms, including neurological disorders. To date, the contributions of and to brain ether lipid production and the molecular mechanism of PFCRD have remained unknown.
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