Chronic neutrophilic leukemia complicated with monoclonal gammopathy of undetermined significance: A case report and literature review

Abstract

Background Study of the molecular biological characteristics of chronic neutrophilic leukemia complicated with plasma cell disorder (CNL‐PCD) and lymphocytic proliferative disease (CNL‐LPD). Methods The clinical data of a patient with chronic neutrophilic leukemia complicated with monoclonal gammopathy of undetermined significance (CNL‐MGUS) in our hospital were reviewed, and the Chinese and/or English literature about CNL‐PCD and CNL‐LPD in PubMed and the Chinese database CNKI in the past 10 years was searched to analyze the molecular biological characteristics of this disease. Results A 73‐year‐old male had persistent leukocytosis for 18 months. The white blood cell count was 46.77 × 109/L and primarily composed of mature neutrophils; hemoglobin: 77 g/L; platelet count: 189 × 109/L. Serum immunofixation electrophoresis showed IgG‐λ monoclonal M protein. A CT scan showed splenomegaly. Next‐generation sequencing (NGS) showed that CSF3R T618I, ASXL1 and RUNX1 mutations were positive. It was diagnosed as CNL‐MGUS. We summarized 10 cases of CNL‐PCD and 1 case of CNL‐LPD who underwent genetic mutation detection reported in the literature. The CSF3R mutational frequency (7/11, 63.6%) was lower than that of isolated CNL. The ASXL1 mutations were all positive (3/3), which may represent a poor prognostic factor. The SETBP1 mutation may promote the progression of CNL‐PCD. We also found JAK2, RUNX1, NRAS, etc. in CNL‐PCD. Conclusions Chronic neutrophilic leukemia may be more inclined to coexist with plasma cell disorder. The CSF3R mutation in CNL‐PCD is still the most common mutated gene compared with isolated CNL. Mutations in SETBP1 and ASXL1 may be poor prognostic factors for CNL‐PCD.

Commentary: Case report: Chronic neutrophilic leukemia associated with monoclonal gammopathies. A case series and review of genetic characteristics and practical management

“…CSF3R mutation in CNL-PCD requires further investigation in more cases. As further mutations were not detected in some of the 16 cases we evaluated, we were unable to accurately calculate the mutation frequencies of additional mutations; however, similar to isolated CNL, we found relatively high mutation frequencies of SETBP1 and ASXL1 in CNL-PCD ( 11 ). The median mutation frequencies of ASXL1 and SETBP1 in isolated CNL are 57.1% and 35.7%, respectively, and these alterations are poor prognostic factors for patients with CNL and CNL-PCD ( 12 ).…”

The impact of SETBP1 mutations in neurological diseases and cancer

“…Association of SETBP1 with mutations other than ASXL1 has also been reported. SETBP1 mutations have been shown to be a poor prognostic factor in chronic neutrophilic leukemia (CNL) which is a rare myeloproliferative leukemia (Gao et al, 2022). Patients with colony‐stimulating factor 3 receptor ( CSFR3 ) mutations, which account for more than half of the CNL patients, have a high frequency of SETBP1 mutations.…”

Chronic Neutrophilic Leukemia: A Comprehensive Review of Clinical Characteristics, Genetic Landscape and Management

“…In order to establish the diagnosis of CNL, other cases of reactive leukocytosis should be excluded. Occasionally CNL has been reported to coexist with lymphoid neoplasms ( 53 ), but the most striking association has been with various plasma cell dyscrasias, such as monoclonal gammopathy of undetermined significance (MGUS) ( 39 , 54 – 58 ), and mainly multiple myeloma. There have been several cases of patients reported to have concurrently or consecutively, these two, apparently different hematological dyscrasias ( 28 , 59 – 71 ).…”