SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells.

[Chidamide Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells from Patients with Myelodysplastic Syndromes].

Objective: To explore the effects and mechanisms of chidamide on the osteogenic differentiation of bone marrow mesenchymal stromal cells (MSC) from myelodysplastic syndromes (MDS).

Methods: MSC were isolated and cultured from bone marrow of MDS patients and healthy donors. CCK-8 assay was used to detect the effects of chidamide on the proliferation of MSC.

deficiency impairs HSPC homeostasis and erythropoiesis via and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 () mutations in patients with MDS, while the exact role of in hematopoiesis remains poorly delineated. Here, we report that deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS.

The bcl6 corepressor mutation regulates the progression and transformation of myelodysplastic syndromes by repressing the autophagy flux.

The occurrence of autophagy dysregulation is vital in the development of myelodysplastic syndrome and its transformation to acute myeloid leukemia. However, the mechanisms are largely unknown. Here, we have investigated the mechanism of the bcl6 corepressor mutation in myelodysplastic syndrome development and its transformation to acute myeloid leukemia.

The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure.

The use of carbon monoxide breath test to detect the effect of iron overload on erythrocyte lifespan in MDS.

Objective: To investigate the effect of iron overload (IO) on red blood cell (RBC) lifespan in MDS patients with the use of carbon monoxide breath test.

Methods: The red blood cell lifespan of 93 patients with myelodysplastic syndrome (MDS) and 22 healthy volunteers in the control group were measured by alveolar gas carbon monoxide (CO) assay, with the detection of liver iron concentration, iron metabolism index, erythropoietin (EPO) concentration, peripheral blood inflammatory cytokines, etc. The MDS patients were divided into the severe IO group, mild IO group and non IO group according to liver iron concentration.

Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia.

Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs.

Dynamics of epigenetic regulator gene BCOR mutation and response predictive value for hypomethylating agents in patients with myelodysplastic syndrome.

Background: BCOR (BCL6 corepressor) is an epigenetic regulator gene involved in the specification of cell differentiation and body structure development. Recurrent somatic BCOR mutations have been identified in myelodysplastic syndrome (MDS). However, the clinical impact of BCOR mutations on MDS prognosis is controversial and the response of hypomethylating agents in MDS with BCOR mutations (BCOR) remains unknown.

[Research Progress in the Role of Tim3/galectin-9 in Hematological Malignancy--Review].

The incidence of hematological malignant tumor is increasing year by year, and seriously affecting the human health. In addition to the traditional radiation and chemotherapy, immunotherapy has achieved a certain effect in the treatment of blood tumor, but it is limited by exhaustion of CD8 T cell. The exhaustion of CD8 T cells is mainly related to the activation of some immune checkpoint inhibitors, such as (Tim3), programmed death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), etc.

Comparative Study on Iron Content Detection by Energy Spectral CT and MRI in MDS Patients.

The purpose of this study was to identify the difference between dual energy spectral computed tomography (DECT) and magnetic resonance imaging (MRI) used to detect liver/cardiac iron content in Myelodysplastic syndrome (MDS) patients with differently adjusted serum ferritin (ASF) levels. Liver and cardiac iron content were detected by DECT and MRI. Patients were divided into different subgroups according to the level of ASF.

Decitabine Induces Change of Biological Traits in Myelodysplastic Syndromes via FOXO1 Activation.

Decitabine (DAC) is considered to be a profound global DNA demethylation, which can induce the re-expression of silenced tumor suppressor genes. Little is known about the function of tumor suppressor gene FOXO1 in myelodysplastic syndromes (MDS). To address this issue, the study firstly investigated differentially expressed genes (DEGs) for DAC treatment in MDS cell lines, then explored the role of FOXO1 through silencing its expression before DAC treatment in MDS.

Integration Analysis of or Mutation With Bone Marrow Blast Can Improve Risk Stratification in the Patients With Lower Risk Myelodysplastic Syndrome.

Despite the improvements in prognostication of the revised International Prognostic Scoring System (IPSS-R) in myelodysplastic syndrome (MDS), there remain a portion of patients with lower risk (low/intermediate risk, LR) but poor prognostics. This study aimed to evaluate the relative contribution of mutational status when added to the IPSS-R, for estimating overall survival (OS) and progression-free survival (PFS) in patients with LR-MDS. We retrospectively analyzed clinical and laboratory variables of 328 patients diagnosed with MDS according to the FAB criteria.

Analysis of the influencing factors related to liver and cardiac iron overload in MDS patients detected by MRI in the real world.

Objectives: We aim to explore and analyze the related influencing factors of liver and cardiac iron overload in MDS patients detected by magnetic resonance imaging (MRI).

Methods: We have detected cardiac T2* and liver T2* by MRI in 105 MDS patients. Among them, 20 patients accepted MRI examination before and after iron chelation therapy (ICT).

[Iron Overload and Immune Inflammatin Are Risk Factors for the Progression of Myelodysplastic Syndrome--Review].

Abstract　　Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders derived from haematopoietic stem and progenitor cells, also is a common malignant hematological diseases. It is characterized by ineffective bone marrow (BM) haematopoiesis, peripheral blood cytopaenias and a risk of progression to acute myeloid leukaemia. Iron overload is caused from transfusion dependence and ineffective hematopoiesis, which seriously affects the survival and prognosis of MDS patients.

A genetic development route analysis on MDS subset carrying initial epigenetic gene mutations.

MDS development is a dynamic process during which the accumulation of somatic mutations leads to specific malignant evolution. To elucidate the differential roles of gene mutations in typical MDS, we used targeted sequencing to investigate clonal patterns from 563 patients and focused on cases (199/563 cases) with initial mutations (ASXL1, DNMT3A and TET2) at MDS diagnosis. The consistency of frequency and distribution in patients with or without aberrant chromosomes suggested early events of these initial mutations.

[Research Advances on Role of Extracellular Vesicles in the Bone Marrow Microenvironment of Patients with Hematological Malignancies--Review].

Bone marrow (BM) microenvironment appears to play an important role in the pathogenesis of hematological malignancies. Apart from soluble factors and direct cell-cell contact, the extracellular vesicles (EVs) were identified as a third mediator for cell communication within BM microenvironment. Recently, more and more evidences have demonstrated that EVs are also involved in the dysregulation of the BM microenvironment in patients with hematological malignancies.

[Effects of Abnormal Iron Metabolism on EPO-STAT5 Signaling Pathway in Anemia Patients].

Objective: To study the effects of iron metabolism abnormality on EPO-STAT5 signaling pathway in anemia patients.

Methods: According to diseases, the patients were divided into 3 groups: lower risk myelodysplastic syndrome (MDS) group (30 cases) including 14 cases of non-iron over load and 16 cases of iron over load, 12 cases of them were treated by iron chelation therapy; anemia of chronic disease (ACD) group (12 cases) and iron deficiency anemia (IDA) group (12 cases). In addition, the healthy control group was selected.

Clinical significance of hyaluronan levels and its pro-osteogenic effect on mesenchymal stromal cells in myelodysplastic syndromes.

Background: Hyaluronan (HA), a major component of the extracellular matrix, has been proven to play a crucial role in tumor progression. However, it remains unknown whether HA exerts any effects in myelodysplastic syndromes (MDS).

Methods: A total of 82 patients with MDS and 28 healthy donors were investigated in this study.

[Expression of Insulin-like Growth Factor Recepter Type I in CD34 Cells of Patients with Myelodysplastic Syndromes].

Objective: To explore the expression level of insulin-like growth facter (IGF-IR) in CD34 cells of patients with myelodysplastic syndromes(MDS).

Methods: Flow cytometry was used to detect the expression of IGF-IR in the CD34 cells of 100 MDS patients and 18 normal controls.

Results: The average IGF-IR expression level in the CD34 cells of 100 MDS patients (41.

[Inhibitory Effect of Decitabine on Proliferation of MDS-L Cells and Its Mechanism].

Objective: To investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism.

Methods: LC-MS/MS method was used to test the blood DAC concentration of 2 groups of MDS patients being treated with DAC 20 and 15 mg/m×5 d. In according to the various blood DAC concentration levels, the MDS-L cells were treated with different DAC dosages for 24, 48, 72 and 96 h, respectively.

[Anti-Tumor Effect of Rigosertib on HEL and K562 Cells and Its Related Mechanism].

Objective: To investigate the effects of rigosertib on the apoptosis, proliferation and cell cycle of HEL and K562 cells.

Methods: The HEL and K562 cells were treated with different concentration of rigosertib at different time points, the cell apoptosis, proliferation and cycle were determined by using flow cytometry with Annexin V/PI double staining, WST-1 method and 7-AAD assay, respectively. Intracellular signaling proteins were detected by flow cytometry (FCM).

MYCN contributes to the malignant characteristics of erythroleukemia through EZH2-mediated epigenetic repression of p21.

MYC proto-oncogene family including c-myc and n-myc (MYCN) are critical for normal cell development and tumorigenesis. Overexpression of c-myc causes acute erythroleukemia in vivo. However, the role of MYCN in acute erythroleukemia remains poorly understood.

Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase.