Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) chacaterized by persistent peripheral blood monocytosis, hypercellular bone marrow and dysplasia at least in one myeloid lineage. CMML shares much of its molecular landscape with other myeloid neoplasms, while differs from others such as chronic neutrophilic leukemia (CNL), given the high frequency of CSF3R mutations in the latter. In this article, we report a case of CSF3R-mutated CMML and dissect this rare entity by reviewing the medical literature, with the intent to understand how this rare mutation shapes CMML\'s clinical and morphological phenotype. CSF3R-mutated CMML emerges as a rare entity meeting the ICC/WHO diagnostic criteria for CMML and simultaneously showing clinical-pathological and molecular traits of CNL and atypical chronic myeloid leukemia, rising an important and difficult diagnostic and therapeutical issue.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) with less than 40 cases of patients being reported or clinically suspected meeting with 2008 World Health Organization (\"WHO\") diagnostic criteria. The current diagnosis of CNL remains to exclude other diseases. Recently, a new biomarker of CSF3R mutations that is almost invariably present in CNL has been identified. There is no effective treatment for CNL, therefore prognosis of the disease is poor, but it may be attributed to the presence of both SETBP1 and CSF3R gene mutations. The presence or absence of CSF3R mutation did not affect survival, whereas a trend for shortened survival was observed among patients with SETBP1-mutation.
Here we report a 65-year old woman patient who presented with leukocytosis without sign of fever and tumors. Bone marrow aspirates showed a markedly hypercellular feature with 76%-92% myeloid and the dysplastic changes were found in about 7% of neutrophils cells. The bone marrow biopsy demonstrated marrow fibrosis with Gomori staining positive (+++~++++). Cytogenetic analysis showed 46,X,del (X) (q22). No molecular markers of BCR/ABL1 rearrangement (P210, P230, P190 and variably), JAK2V617F, FIP1L1-PDGFRA, TEL-PDGFRB, ZNF198-FGFR1 and SETBP1 mutations were identified, however, the CSF3R gene membrane proximal mutation (c.1853C > T/p.T618I sites) was detected by PCR techniques. The patient was diagnosed with CNL and died in about 2 months after disease diagnosis.
In clinical course, the CNL concurrently with severe bone marrow fibrosis and dysplastic features as well as X chromosomal abnormality may predict a worsening prognosis regardless of SETBP1 mutation status.

OBJECTIVE: To explored the diagnosis and treatment of chronic neutrophilic leukemia (CNL) complicated with multiple myeloma (MM).
METHODS: The clinical features and molecular biological characteristics of 2 patients with CNL complicated with MM were summarized, and the diagnosis and treatment of the patients were retrospectively reviewed.
RESULTS: The diagnosis of CNL complicated with MM was established in 2 cases. Case 1 had CSF3R mutation (P733T), but CSF3R-exon 14 mutation and SETBP1 mutation were all negative. The neutrophil count returned to normal when MM was successfully treated in case 1. When the patient relapsed, neutrophil count increased again.
CONCLUSIONS: Coexistence of CNL and MM is rare. CSF3R is a very important molecular marker for CNL. To the best of our knowledge, it\'s the first time to report the coexistence of CNL and MM carried CSF3R mutation (P733T). Chemotherapy regimens for MM may be effective in the treatment of CNL complicated with MM.

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient\'s prognosis.

CSF-1 (colony stimulating factor-1), initially considered to be a monocyte specific growth and differentiation factor [4], has recently been shown to be produced in human endometrium [16], placenta [7], as well as in numerous solid tumors [19-23, 26, 27]. The CSF-1 receptor (a protein product of c-fms) [24] is a member of the tyrosine kinase receptor family and an autocrine or paracrine mechanism of activation has been suggested. Overactivation of this receptor can lead to a malignant phenotype in various cell systems [20, 21]. We review the biology of CSF-1 and fms expression in normal as well as in malignant tissues with particular reference to a potential role for CSF-1 in breast tumour invasion.

Both structure-function analysis of hematopoietic growth factor receptors and identification of novel signal transduction molecules have provided new insights into the processes involved in signal transmission pathways engaged by hematopoietic growth factors. These investigations have pointed to the importance of post-translational modifications of pre-existing proteins, in particular tyrosine phosphorylation, in transmitting signals and thereby linking extracellular signals to the activation of nuclear effector molecules which govern gene expression. These observations not only contribute to our understanding of the pleiotropism and redundancy ascribed to hematopoietic growth factors, but also help to trace some of the molecules conferring signal specificity. It is to be expected that this rapidly evolving research field will provide us with a significant collection of new findings in the near future and that the precise understanding of the processes involved in ligand-binding and signal transmission will also stimulate the development of novel therapeutic drugs affecting these processes. This article gives a short overview on the role of tyrosine kinases and their substrates in signal transmission processes initiated by hematopoietic growth factors.

暂无摘要。