Epigenomics ; Hematologic Diseases ; genetics ; Humans

Humans ; Child ; High-Throughput Nucleotide Sequencing ; Consensus ; Hematologic Diseases/genetics*

This article summarizes the progress of hematology in the recent tens years to show that experimental hematology used to pick up the 'hints' from clinical problems as the renewal of research directions and targets in experimental studies continuously. As the feedback, the results from lab investigations inserted into clinical practice and eventually made a quick modernization of hematology, which was actually a good model for the "translational research". The past few decades have witnessed tremendous advances in our understanding of normal hematopoiesis where genes dictate, epigenetics regulate, transcription factors mediate, and stem cells self-renew and differentiate. Dissection of disease pathogenesis not only elucidates molecular basis of disorders including hemoglobinopathy, aplastic anemia, hemophilia, hematopoietic malignancies such as leukemia and myeloproliferative disorders, but also provides therapeutic targets for drug development. Introduction of targeted therapies and combinatory targeting therapies greatly benefits hundreds of thousands of patients, and even turns acute promyelocytic leukemia from highly fatal to highly curable. In the 21st century the experimental hematology is entering the era of genomics and system biomedicine, and the pace of progress extrapolates to a prediction of hematologic neoplasms control in this century.
Animals ; Clinical Laboratory Techniques ; trends ; Hematologic Diseases ; genetics ; metabolism ; physiopathology ; Hematologic Neoplasms ; genetics ; metabolism ; physiopathology ; Hematology ; trends ; Humans

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

Signal transducer and activator of transcription 5 (STAT5) is an important transcription factor existing in the cytoplasm of various types of cells. Once activated, STAT5 dimers translocate into nucleus and bind to the corresponding DNA sequence to regulate the transcription of its target genes. There are two isoforms of STAT5: STAT5A and STAT5B with 96% sequence homology and are encoded by two closely related but different genes. Studies have shown that STAT5 can regulate the survival, proliferation, differentiation and death of hematopoietic cells. Furthermore, elevated activation of STAT5 was found in many malignant hematologic diseases and therefore raised the possibility that STAT5 may be used as a new therapeutic target for blood related diseases. This review discusses the regulatory role of STAT5 in hematopoietic cells and its effect on the occurrence and development of blood diseases.
Animals ; Hematologic Diseases ; genetics ; metabolism ; Hematopoietic System ; metabolism ; Humans ; STAT5 Transcription Factor ; genetics ; metabolism

OBJECTIVE: To observe the expression level of serum homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in patients with hematological diseases complicated with coronary heart disease, and analyze the relationship between serum Hcy level, MTHFR gene polymorphism and coronary heart disease. METHODS: The medical records of 80 patients with coronary heart disease who completed treatment of hematological diseases during the period from March 2018 to March 2020 were selected as observation group. In addition, the medical records of 92 patients with hematological diseases who completed treatment in our hospital during the same period were selected as control group. Venous blood samples of the two groups were collected to detect serum Hcy level and MTHFR gene polymorphism. The serum Hcy levels of the two groups with different MTHFR genotypes were compared, and the effects of the above indicators on hematological diseases complicated with coronary heart disease were analyzed. RESULTS: The detection rates of MTHFR gene TT and TC in the observation group were higher than those in the control group, while the distribution frequency of MTHFR genotype CC was lower (P<0.05). The serum Hcy levels of the patients with MTHFR genotype TT and TC in the observation group was higher than the control group (P<0.05). Binary logistic regression analysis showed that MTHFR gene TC/CC genotype serum Hcy overexpression may be influencing factor which induced coronary heart disease in patients with hematological diseases (OR=2.107/OR=1.634, P<0.05). ROC curves showed that the AUC of serum Hcy level of MTHFR gene TC/CC genotype and hematological disease complicated with coronary heart disease were both > 0.8. When MTHFR gene TC reaching the optimal threshold of 22.165 μmol/L, the sensitivity was 0.950 and the specificity was 0.837, While MTHFR gene CC reached the optimal threshold of 19.630 μmol/L, the sensitivity was 0.938 and the specificity was 0.826, the best predictive value could be obtained. CONCLUSION The changes of serum Hcy and MTHFR gene polymorphisms may be involved in the pathological process in patients with hematological diseases complicated with coronary heart disease. In the future, early detection of serum Hcy levels and MTHFR gene polymorphisms in patients with hematological diseases can be used to predict the risk of coronary heart disease.
Coronary Disease/genetics* ; Genotype ; Hematologic Diseases/complications* ; Homocysteine ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Polymorphism, Genetic

The TET gene family has been found a few years ago. Recent studies indicated that TET2 (TET gene family 2) plays an important role in DNA demethylation, the epigenetic regulation and normal hematopoiesis. TET2 mutation has been discovered in a spectrum of myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and leukemia, which suggest the role of TET2 as a tumor suppressor. In this review the recent results implicating TET2 in hematological malignancies are summarized, including regulatory functions of TET gene epigenetics, TET2 gene and hematopoietic regulation in bone marrow, TET2 gene and hematological disease(MPN, MDS, AML, CMML, lymphoma) and so on.
Bone Marrow ; metabolism ; DNA-Binding Proteins ; genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Hematologic Diseases ; genetics ; Humans ; Proto-Oncogene Proteins ; genetics

OBJECTIVE: To investigate the correlation between the production of platelet HLA-Ⅰ antibody and HLA-A, B genes in patients with malignant hematological diseases, and explore the susceptible gene for producing platelet HLA-Ⅰ antibody. METHODS: Patients with malignant hematological diseases who had received multiple platelet transfusion were selected as the research objects in the Department of Hematology of our hospital. Platelet HLA-I antibody were screened by ELISA, and the patients were divided into positive and negative groups according to the results. HLA-A and B genes were sequenced after genomic DNA was extracted, and the frequencies of them were compared between the two groups. RESULTS: The positive rate of platelet HLA-I antibody was 22.95%. A total of 13 HLA-A alleles and 14 HLA-B alleles were obtained after the HLA-A and B genes sequencing in 100 cases. The frequencies of HLA-A*24, HLA-A*30, and HLA-B*13 were significantly different between the two groups (P<0.05). Frequencies of HLA-A*30 and HLA-B*13 in the positive group were lower than those in the negative group (RR=0.107, 0.387), but HLA-A*24 was higher (RR=1.412). After high-resolution typing of HLA-A*24, HLA-A*30, and HLA-B*13, frequencies of HLA-A*24∶02, HLA-A*30∶01, and HLA-B*13∶02 were significantly different between the two groups, the RR value was 1.412, 0.107, and 0.125, 95%CI was 0.961-2.075, 0.016-0.721, and 0.300-0.515, respectively. CONCLUSION HLA-A*24∶02 may be a susceptible gene for producing platelet HLA-Ⅰ antibody in patients with malignant hematological diseases, while HLA-A*30∶01 and HLA-B*13∶02 may be two protective genes.
Alleles ; Antibodies ; Gene Frequency ; HLA-A Antigens/genetics* ; HLA-B Antigens/genetics* ; Hematologic Diseases/genetics* ; Humans ; Platelet Transfusion

OBJECTIVE: To explore the genetic basis of a child with recurrent infection, multiple malformation and dysmorphism. METHODS: The child and his parents were subjected to trio whole exome sequencing. RESULTS: The child had a complaint of fever and cough, with long and thin eye fissures and long eyelashes. Genetic testing revealed that the child has carried a non-triplet deletion of the KDM6A gene, which was unreported previously. The variant resulted in frameshift and premature termination of the translation. His parents were both of the wild type for the locus. After antibiotic and immunoglobulin treatment, the severe secondary pneumonia caused by immunodeficiency has improved. CONCLUSION With combined laboratory test, imaging examination and genetic testing, the child was ultimately diagnosed with Kabuki syndrome type 2. The characteristics of immunodeficiency of Kabuki syndrome may render conventional antibiotic treatment ineffective, which deserves clinical attention.
Abnormalities, Multiple ; Child ; DNA-Binding Proteins/genetics* ; Face/abnormalities* ; Genetic Testing ; Hematologic Diseases ; Histone Demethylases/genetics* ; Humans ; Neoplasm Proteins/genetics* ; Nuclear Proteins/genetics* ; Phenotype ; Pneumonia ; Vestibular Diseases

Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (C_trough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The C_trough of the 65 patients were detected for 169 times totally, and there was a significant difference of C_trough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of C_trough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ²=11.689, P=0.020). Conclusion: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their C_trough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.
Antifungal Agents ; Cytochrome P-450 CYP2C19/genetics* ; Genotype ; Hematologic Diseases/genetics* ; Humans ; Mycoses ; Phenotype ; Polymorphism, Genetic ; Voriconazole