Humans ; Mutation ; Myelodysplastic-Myeloproliferative Diseases ; diagnosis ; genetics

OBJECTIVETo screen signaling pathway proteins in myelodysplastic/myeloproliferative neoplasms-unclassifiable (MDS/MPN-U), and to explore the possible role of the differentially expressed signaling pathway proteins in pathogenesis of MDS/MPN-U.

METHODSProtein Pathway Array (PPA) was applied to analyze the differential expression levels of signaling pathway proteins in 10 patients with MDS/MPN-U and normal controls, and furthermore to identify the signaling pathways and network in which these proteins were analyzed by Ingenuity pathway analysis program.

RESULTSThe expressions of 25 signaling proteins in MDS/MPN-U were significantly different, compared with the control group. Among them 15 proteins were upregulated in MDS/MPN-U patients, while 10 proteins were downregulated. These dysregulated proteins were involved in 10 major signaling pathways related with cell proliferation and immunity. The complicated interactive network was established by these proteins and pathways.

CONCLUSIONThe differentially expressed signaling proteins screened from the MDS/MPN-U patients by PPA might be helpful to reveal the pathogenesis of MDS/MPN-U and to discover the therapeutic targets.

OBJECTIVE: To investigate the clinical significance of the targeted next-generation sequencing assay for patients with suspected myeloid malignancies. METHODS: A total of 39 hematopenia patients with suspected myeloid malignamies in Department of Hematology of The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2018 to April 2019 were treated, 20 hot spot genes of myelodysplastic syndrome (MDS) were detected. RESULTS: Regarding the diagnostic type, there were 7 cases of idiopathic cytopenia of undetermined significance (ICUS), 8 cases of clonal cytopenias of undetermined significance (CCUS) and 24 cases of myeloid myeloid malignancies which included 18 cases of MDS, 4 cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 2 cases of acute myeloid leukemia. Positive mutation was detected in 70.8% (17/24) of myeloid malignancy patients , and 72.7% (16/22) in MDS and MDS/MPN patients. The main mutation types were ASXL1, TET2 and RUNX1. Compared with gene negative group, there were no significant differences in sex, age (＜60 years old or ≥60 years old), proportion of bone marrow blast cells (＜5% or≥5%) and cytogenetics (good, medium and poor) (P＞0.05). Furthermore, all 8 CCUS patients showed positive mutation, and the incidence of double or multiple mutation in CCUS group was significantly lower than that of the MDS and MDS/MPN group (37.5% vs 54.5%) (P=0.002). The mutation types between the two groups were similar, and there was no significant difference in variant allele frequency (P＞0.05). CONCLUSION Our results suggest that there are high rates of double or multiple mutations in myeloid malignancies, especially in patients with MDS and MDS/MPN. Targeted sequencing assay can improve the diagnosis of myeloid malignancies, and guide clinical treatment.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Myelodysplastic Syndromes/genetics* ; Myelodysplastic-Myeloproliferative Diseases ; Patients

Chronic myeloproliferative disease (CMPD) is a group of malignant blood disorders including polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic myeloid leukemia, and so on. CMPD is characterized by proliferation of one or several lineages in hematopoietic system. The pathogenesis of CMPD is not clear except chronic myeloid leukemia associated with the bcr/abl fusion gene. In recent years, more studies demonstrated that CMPD have a higher mutation rate of gene jak2. In this review, the association of jak2 gene mutation with clinical diagnosis, clinical feature and molecular target therapy in CMPD and other hematological disease were summarized.
Chronic Disease ; Humans ; Janus Kinase 2 ; genetics ; Mutation ; Myelodysplastic-Myeloproliferative Diseases ; genetics

Abstract　　Single cell sequencing technology is different from traditional sequencing method, which is based on population cell average level. It has been widely used in many fields and made great progress in the application of malignant hematological diseases. In this review, the principle, methodology and application of single cell sequencing technology in malignant hematological diseases are summarized briefly, including the study of the pathogenesis in myelodysplastic syndrome, the mechanism of transformation into leukemia, accurate diagnosis and classification, differential diagnosis, evaluation of targeted drug therapeutic efficacy and exploration of biomarkers; specific diagnostic indicators for myeloproliferative diseases, progression of disease monitoring and epidemiological studies; moreover, the pathogenesis and drug resistance of acute myeloid leukemia (AML), which can provide reference for the diagnosis and research of malignant hematological diseases.
Hematologic Diseases ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Myeloproliferative Disorders ; Sequence Analysis

This study aimed to investigate the relationship between clinical features of myelodysplastic/myeloproliferative disease, unclassifiable (MDS/MPD-U), karyotype of chromosome and JAK2 mutation in 1 case. The clinical features, karyotype and JAK2 mutation of the patient with MDS/MPD-U were studied by means of bone marrow biopsy, karyotype analysis and ARMS-PCR technique. The results indicated that the typical micromegakaryocytes and thrombocytosis, karyotype aberration of trisomy 8 as well as JAK2 V617F mutation were found in this patient. It is concluded that the patient was diagnosed as MDS/MPD-U with trisomy 8 and JAK2 V617F mutation. The data of this patient will provide evidence for studying correlation of chromosome karyotype aberration with JAK2 V617F mutation and for evaluating prognosis of MDS/MPD-U.
Chromosomes, Human, Pair 8 ; Female ; Humans ; Janus Kinase 2 ; genetics ; Karyotyping ; Middle Aged ; Mutation ; Myelodysplastic-Myeloproliferative Diseases ; classification ; genetics ; Trisomy

Tet2 (the 2nd member of tet oncogene family) is a newly discovered antioncogene on the chromosome 4q24 of the patient with malignant myeloma, which has a potential for functional deletion. Recent studies demonstrated that tet2 mutation was found in polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis, systematic mastocytosis (SM), and myelodysplastic syndrome (MDS). However, a great number of perspective researches are still needed for exploring the role of tet2 in the pathogenesis of malignant blood diseases. In this review, the relation of tet2 mutation with myeloproliferative neoplasm, systemic mastocytosis, myelodysplastic syndrome, acute myeloid leukemia and other malignant blood diseases are summarized.
DNA-Binding Proteins ; genetics ; Hematologic Diseases ; genetics ; Humans ; Mutation ; Myelodysplastic Syndromes ; genetics ; Myeloproliferative Disorders ; genetics ; Proto-Oncogene Proteins ; genetics

Anemia, Sideroblastic ; genetics ; Calreticulin ; genetics ; Humans ; Mutation ; Myelodysplastic-Myeloproliferative Diseases ; genetics ; Phosphoproteins ; genetics ; RNA Splicing Factors ; Ribonucleoprotein, U2 Small Nuclear ; genetics

This study was purposed to explore the therapeutic efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) and in patients with juvenile myelomonocytic leukemia (JMML). The clinical data of 3 cases of CMML and 2 cases of JMML underwent allo-HSCT were analysed in term of multiparameter. The results showed that the hematopoietic stem cells in 5 patients grafted successfully. One case of JMML died of pulmonary disease, other 4 cases survive without disease. The analysis found that the disease burden before transplant, chromosome karyotype, acute GVHD II-IV and poor risk cytogenetics all associated with the relapse rate and disease-free survival rate of CMML. The low intensity conditioning regimen was better than myeloablative conditioning regimen. Type of donor and source of stem cells did not statistically and significantly affect OS and RFS. The splenectomy before allo-HSCT as well as spleen size at time of the alloHSCT did not influence on posttransplantation outcome of JMML. However, cord blood HSCT for JMML patients delayed hematologic recovery as compared to that of bone marrow or peripheral blood HSCT. The age, GVHD, HbF level played an important role in leukemia replace. It is concluded that the allogeneic hematopoietic stem cell transplantation is a curative regimen for CMML and JMML, but there also is a serial problems to be resolved.
Adult ; Child, Preschool ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Leukemia, Myelomonocytic, Chronic ; therapy ; Leukemia, Myelomonocytic, Juvenile ; therapy ; Male ; Middle Aged ; Transplantation, Homologous ; Treatment Outcome

BACKGROUND: In adults, the 2 main types of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML). Both are associated with a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) is the only known curative treatment modality for these diseases, but data on outcomes following such treatment are limited. We analyzed the outcomes of patients with MDS/MPN after allogeneic HCT. METHODS: This retrospective study included 10 patients with MDS/MPN who received allogeneic HCT at Asan Medical Center from 2002 to 2010. Of these 10 patients, 7 had CMML, 2 had aCML, and 1 had unclassifiable MDS/MPN. Five patients received a myeloablative conditioning (MAC) regimen (busulfan-cyclophosphamide), and 5 received reduced-intensity conditioning (RIC) regimen. RESULTS: Neutrophil engraftment was achieved in all patients. After a median follow-up of 47.5 months among surviving patients, 4 had relapsed and 5 had died. There was only 1 treatment-related death. The 5-year rates of overall, relapse-free, and event-free survival were 42.2%, 51.9%, and 46.7%, respectively. Relapse was the leading cause of treatment failure, and all relapses were observed in patients who had received RIC and who did not develop chronic graft-versus-host disease. CONCLUSION: Allogeneic HCT can induce durable remission in patients with MDS/MPN, but RIC cannot replace MAC in patients eligible for myeloablative treatments.
Adult ; Cell Transplantation ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ; Leukemia, Myelomonocytic, Chronic ; Neutrophils ; Prognosis ; Recurrence ; Retrospective Studies ; Transplants ; Treatment Failure