DNA methylation is an important and reversible epigenetic modification which regulates genomic stability. Methylation is essential for mammalian development. Generally, gene expression level and DNA methylation are negative correlation. Transcriptional silencing via methylation of CpG islands in the promoter is important for cell growth and differentiation and plays a key role in tumorigenesis. Demethylation drug can modify chromatin and restore the ability of anti-oncogene. Demethylation therapy as a new therapy may treat efficiently hematological malignancies with resistance and relapse. In this review, DNA methylation mechanism, relationship between aberrant methylation and hematologic malignancies, mechanism of demethylation therapy, the advance of research on the demethylation therapy of hematological malignancies, such as acute and chronic leukemia, lymphoma, myelodysplastic syndrome were summarized.
DNA Methylation ; Hematologic Neoplasms ; genetics ; metabolism ; therapy ; Humans ; Methylation

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

N6-methyladenosine (m6A) is one of the most common epigenetic modifications of eukaryotic mRNAs, which is involved in the regulation of gene expressions and biological processes in a variety of cells with dynamic and reversible methylation processes. In recent years, many studies have shown that m6A methylation modification not only acts on the growth, proliferation, and medullary differentiation of acute myeloid leukemia cells, but also participates in the regulation of the proliferation and apoptosis of other hematological tumor cells such as chronic myeloid leukemia and diffuse large B-cell lymphoma, and it can even weaken the efficacy of anti-hematological tumor immunotherapy and induce immune escape leading to tumor resistance. With the successive development of a variety of m6A methylation-related enzyme inhibitors, it will provide new therapeutic ideas for patients with relapsed and refractory hematological tumors. In this paper, we review the research progress on the mechanism of m6A methylation on the occurrence, development, and tumor immunity of various hematological tumors.
Adenosine/metabolism* ; Epigenesis, Genetic ; Hematologic Neoplasms/genetics* ; Humans ; Methylation ; Neoplasms/metabolism* ; RNA, Messenger/metabolism*

Rap1 is a small G protein belonging to the RAS superfamily. Rap1 signalling has effects on cell growth, cell proliferation and involves in regulation of the mitogen activated protein (MAP) kinase or ERK (extracellular signal regulated kinase) cascade. Rap1 will directly activate ERK through B-Raf. B-Raf is a member of Raf family, and presents in neuronal and hematopoietic cells. Oncogenic mutations of gene RAS are most frequent and detected in 20% - 30% of human leukemias and 10% - 15% of MDS cases. The review summarizes the regulatory function of Rap1 in development of hematopoietic cells and effect of Rap1 in hematologic malignancies.
Hematologic Neoplasms ; genetics ; metabolism ; Humans ; Signal Transduction ; rap1 GTP-Binding Proteins ; genetics ; metabolism

The microRNAs (miRNAs) are an evolutionarily conserved class of 22 nucleotide (19 - 25 nt) non-coding RNAs. The miRNAs are partially complementary to 3' untranslated region of target mRNA, resulting in the repression of gene expression at post-transcriptional level. The miRNAs have been associated with diverse biological processes. This review summarizes recent progress of research on the characteristics and function of miRNAs, and the role of miRNAs in hematological malignancy development.
Gene Expression Regulation, Neoplastic ; genetics ; Hematologic Neoplasms ; genetics ; metabolism ; Humans ; MicroRNAs ; genetics ; physiology

Animals ; Gene Expression Profiling ; Gene Silencing ; Hematologic Neoplasms ; genetics ; metabolism ; Hematopoiesis ; genetics ; Humans ; MicroRNAs ; metabolism ; physiology ; Neoplasms ; genetics ; metabolism ; Oligonucleotide Array Sequence Analysis ; T-Lymphocytes ; metabolism

The sex-determining region Y-box 7 (Sox7) is a important member of SOX family containing high mobi- lity group (HMG), mapped to human chromosome 8p23.1. Wnt/β-catenin signaling pathway plays an important role in cell survival, differentiation, self-renewal, proliferation and apoptosis, and is closely related with carcinogenesis. SOX7 gene is likely to be a tumor suppressor gene in MDS and other hematological malignancies. As a negative regulator of the WNT/β-catenin signaling pathway, the function loss of this gene can lead to carcinogenesis. The methylation of SOX7 gene leads to the silence of this gene, resulting in tumorigenesis. The decision of hematopoietic stem cells to self-renew or differentiate is a stochastic process, but SOX7 can promote the differentiation into all blood cell types. This review focuses on the role of SOX7 in hematopoietic system development and hematological malignancies.
DNA Methylation ; Gene Silencing ; Hematologic Neoplasms ; genetics ; metabolism ; Hematopoietic System ; physiopathology ; Humans ; SOXF Transcription Factors ; genetics ; metabolism ; Wnt Signaling Pathway

This study was purposed to investigate the killer immunoglobulin-like receptor (KIR) genotype in patients with hematological malignancies. The sequence specific primer-polymerase chain reaction (PCR-SSP) technique was performed for the amplification of six inhibitory KIR genes (KIR2DL1-2DL4, 3DL1-3DL2) and six activating KIR genes (KIR2DS1-S5, 3DS1). The methods of KIR-SSP was used to determine the KIR genotypes of 54 leukemia patients, including 14 patients with acute myeloid leukemia (AML), 16 with acute lymphoblastic leukemia (ALL), 20 with chronic myeloid leukemia (CML), 3 with myelodysplastic syndrome (MDS) and 1 with acute myeloid-lymphoblast leukemia (AMLL). 54 patients were classified as high risk group (n = 27) and standard risk group (n = 27). The expression of KIR in NK cells and T cells was detected by flow cytometry. The frequencies of activating KIR genes in standard risk group were higher than those in high risk group, especially 2DS1 (p = 0.014), or 2DS2 (p = 0.046), or 3DS1 (p = 0.027). However, the frequencies of inhibitory KIR genes in standard risk group were similar to those in high risk group (p > 0.05). The frequencies of activating KIR genes were also higher in standard risk patients with acute AML, as compared with those in high risk patients with acute AML, particularly 2DS1 (66.7% vs 29.4%, p = 0.022), 2DS2 (57.6% vs 17.6%, p = 0.013), and 2DS3 (33.3% vs 5.9%, p = 0.039). The percentages of patients in high-risk group who expressed more than two kinds of activating KIRs were lower that those in standard-risk group (p = 0.035). There was no difference in the expressions of CD158a, CD158b, and CD158e on NK cells and T cells between high-risk group and standard-risk group (p > 0.05). In conclusions, different expressions of activating KIR genes were found in patients between high-risk group and standard-risk group.
Genotype ; Hematologic Neoplasms ; genetics ; immunology ; Humans ; Killer Cells, Natural ; immunology ; metabolism ; Receptors, KIR ; genetics ; Risk Factors ; T-Lymphocytes ; immunology ; metabolism

Long non-coding RNA (lncRNA) is a hot topic in the field of researching tumor pathogenesis, and the importance in hematologic malignancies has been gradually being elucidated. LncRNA not only regulates hematological tumorigenesis and progression through affecting various biological processes such as cell proliferation, differentiation, pluripotency and apoptosis; moreover, abnormal expression and mutation of lncRNA are closely related to drug resistance and prognosis. Thus lncRNA can be used as novel biomarker and potential therapeutic target for hematological tumors. In this review, we will focus on the latest progress of lncRNA in hematological tumors to provide new ideas for the clinical diagnosis, prognostic evaluation together with research and development of target drugs for hematologic malignancies.
Humans ; RNA, Long Noncoding/metabolism* ; Hematologic Neoplasms/genetics* ; Neoplasms ; Carcinogenesis/pathology* ; Cell Transformation, Neoplastic/genetics* ; Gene Expression Regulation, Neoplastic

Nucleophosmin (NPM) is a protein that shuttles between the nucleus, nucleoplasm and cytoplasm. NPM gene mutations and aberrant cytoplasmic NPM localization have been recently described in acute myelogenous leukemia (AML) with normal karyotype and in a few myelodysplastic syndromes. Expression of NPM mutant reduces the ability of Arf to initiate a p53 response and to induce cell cycle arrest. Clinical research has revealed that NPM mutations are relative to prognosis and can be used to monitor and quantify minimal residual disease (MRD) in AML patients with normal karyotype, therefore, these findings indicate that nucleophosmin mutations might contribute to illustration of myeloid leukemogenesis. In this paper, the research progress of nucleophosmin mutations in haematological malignancies was reviewed.
Cell Nucleolus ; metabolism ; Hematologic Neoplasms ; genetics ; pathology ; Humans ; Mutation ; Nuclear Proteins ; genetics ; fms-Like Tyrosine Kinase 3 ; genetics