Influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome: A retrospective study / 中华血液学杂志

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.

Research Progress in the Role of Tim3/galectin-9 in Hematological Malignancy--Review / 中国实验血液学杂志

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

Research Advances on Role of Extracellular Vesicles in the Bone Marrow Microenvironment of Patients with Hematological Malignancies--Review / 中国实验血液学杂志

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. Therefore this review focuses on the biological characteristics of EVs, the clinical value of EVs as biomarkers, the BM microenvironment reprogramming in hematological malignancies by EVs, and the potential role of EVs in drug resistance and therapy of hematological malignancies.

Prognostic scoring of myelodysplastic syndromes / 天津医药

@#Myelodysplastic syndrome (MDS) is a clonal disease derived from the hematopoietic stem cells, with a high degree of heterogeneity and complexity. The prognostic evaluation of MDS is a core problem of this disease, mainly because the complex pathogenesis (genomics, epigenetics, bone marrow microenvironment and immune factors) determines the heterogeneity of clinical characteristics (heterogeneity of age, infection, risk of bleeding, and comorbidities) and differential clinical outcome (bone marrow failure and leukemia transformation). Therefore, how to comprehensively consider various prognostic factors to establish a prognostic score system to predict the prognosis and clinical outcome of patients with MDS is very important. In the past two decades, many MDS scholars have devoted themselves to the study of various MDS prognostic scoring systems. Typical prognostic scoring systems such as the International Prognostic Scoring System (IPSS) and its revisions (IPSS-R) have been widely used. In addition, based on these new prognostic factors, the prognostic scoring system has also showed good prognostic value with the discovery of many clinical markers and molecular changes. This review summarizes the prognostic scoring system and new prognostic factors of MDS in recent years for reference in clinical practice.

Expression of Insulin-like Growth Factor Recepter Type I in CD34 Cells of Patients with Myelodysplastic Syndromes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the expression level of insulin-like growth facter (IGF-IR) in CD34 cells of patients with myelodysplastic syndromes(MDS).</p><p><b>METHODS</b>Flow cytometry was used to detect the expression of IGF-IR in the CD34 cells of 100 MDS patients and 18 normal controls.</p><p><b>RESULTS</b>The average IGF-IR expression level in the CD34 cells of 100 MDS patients (41.0±28.1)% was statistically and significantly elevated in comparison with the corresponding level in normal controls(4.3±1.8)%,(P<0.0001). The average expression level of 22 cases in high-risk groups was very significantly increased, compared with that in 78 cases of low-risk groups[(66.5±27.8)% vs (34.5%±24.9)%](P<0.0001), and the average expression level in 23 patients with chromosome abnormality was very significantly increased in comparison with that in rest 77 patients [(56.0±30.9)% vs (36.9%±26.2)%](P<0.01).</p><p><b>CONCLUSION</b>The over-expression of IGF-IR in CD34 cells of MDS patients suggests that the IGF-IR may involve in the origin, occurrence and progress. The average IGF-IR expression level is markedly elevated in high-risk groups and the patients who showed chromosome abnormality, this trend revealed that IGF-IR correlates with malignant clonal proliferation in MDS patients, thus providing a basis for their prognosis and outcome evaluation.</p>

Effects of Abnormal Iron Metabolism on EPO-STAT5 Signaling Pathway in Anemia Patients / 中国实验血液学杂志

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. The iron metaloslism index (SF, SI, TIBC), serum level of EPO, plasma level of P-STAT5 and STAT-5 mRNA expression in peripheral blood cells were detected and compared in different groups. Moreover, the effects of iron metabolism abnormality on the expression of EPO and STAT5 in anemia patients were analyzed.@*RESULTS@#compared with non-iron over load group, the EPO level in iron over load group significantly increased (P<0.05), the expression of STAT5 mRNA and P-STAT5 significantly decreased (P<0.05). After iron chelation therapy, the EPO level in serum significantly decreased (P<0.05), the expression of STAT5 mRNA and P-STAT5 was up-regulated significantly (P<0.05). Compared with healthy control group, the expression of EPO in ACD group was down-regulated significantly, while the expression of STAT5 mRNA was not different, but the P-STAT5 expression was down-regulated significantly (P<0.05). Compared with the healtly control group, the EPO expression in IDA group was enhanced significantly (P<0.05), the expression of STAT5 mRNA and P-STAT5 were also significantly enhanced (P<0.05).@*CONCLUSION@#The excessive iron load or chronic inflammation may inhibit the activation of EPO-STAT5 signaling pathway and aggravate the anemia.

Anti-Tumor Effect of Rigosertib on HEL and K562 Cells and Its Related Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of rigosertib on the apoptosis, proliferation and cell cycle of HEL and K562 cells.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>Rigosertib induced obvious apoptosis in HEL and K562 cells, and the apoptotic effect was both time-dependent and dose-dependent manner (P<0.05). The low dose of rigosertib inhibited obviously the proliferation of HEL and K562 cells after treatment from 6 to 54 h, Rigosertib arrested HEL and K562 cells into G/M phase. In addition, Rigosertib obviously increased the expression of apoptosis-related proteins such as cleaved caspase 3 and PARP, and reduced the proliferation-related proteins such as BCL-2 and Cyclin D1. Rigosetib inhibited the activation of AKT-GSK signaling through decreasing the expression of AKT, pAKT(Ser473) and GSK-3α/β (S21/9).</p><p><b>CONCLUSION</b>Rigosertib inhibites proliferation, induces apoptosis and cell cycle arrest in G/M phase of HEL and K562 cells. This agent may have potential application prospect in leukemia therapy.</p>

Inhibitory Effect of Decitabine on Proliferation of MDS-L Cells and Its Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism.</p><p><b>METHODS</b>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. The CCK-8 method was applied to determine the cell proliferation, the flow cytometry was used to analyze the cell cycle and cell apoptosis changes, the P15DNA methylation status was measured by methylation specific PCR using EZ DNA Methylation-Gold Kit.</p><p><b>RESULTS</b>The blood DAC concentration of MDS patients treated with DAC 20 mg/m×5 d was 174.08±80.15(84.7-311) ng/ml, which was significantly higher than 89.87±32.94(43.2-165)ng/ml for the group treated with 15 mg/m×5 d (P=0.014). DAC could notably inhibit the proliferation of MDS-L cells, and the effect was in dose- and- time-dependent manner(r=0.786). However, when DAC concentration was ≥0.1 µg/ml, the proliferation inhibition rates were not significantly different between various dosages. After DAC treatment, MDS-L cells in Gphase increased notably, while cells in S phase decreased significantly. Also, the P15DNA methylation status of MDS-L cells decreased after being treated with DAC for 96 h, but the difference was not significant between various dosages.</p><p><b>CONCLUSION</b>DAC can significantly suppress MDS-L cell proliferation, block MDS-L cells in Gphase and induce the apoptosis at low concentration (0.1-0.2 µg/ml).</p>

Underlying Mechanisms of Iron Overloading in Myelodysplastic Syndrome -Review / 中国实验血液学杂志

Myelodysplastic Syndromes(MDS) comprise a heterogenous group of hematopoietic stem cell malignancies characterized by peripheral cytopenias and have a substantial risk of progression to acute myeloid leukemia(AML). MDS, without effective cure methods, is one of the common hematologic malignant tumors with great threaten to people's health. The phenomenon of iron overloading is common in MDS, which has a poor effect on overall survival and leukemic progression to MDS but get good prognosis by iron chelation therapy. Therefore, increasing researchers are interested in iron overloading of MDS. So far, many researchers have reported that blood transfusion, ineffective hematopoiesis, genetic changes, mitochondrial apoptosis and ROS were found to be important in the incidence of iron overloading. There is greatly valuable to guide iron chelation therapy to study the relationship between those elements with iron overloading. In this paper, we reviewed the great important and specific influence of blood transfusion, ineffective hematopoiesis, genetic changes, mitochondrial apoptosis and ROS in the mechanism of iron overloading, which there is a great significance on iron overloading- associated MDS.

Osteogenic Differentiation Potential of Bone Marrow Mesenchymal Stem Cells in Patients with Myelodysplastic Syndromes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMMSC) in patients with myelodysplastic syndromes (MDS) and to explore the role of BMMSC osteogenic differentiation in the pathogenesis of MDS.</p><p><b>METHODS</b>BMMSC were isolated from bone marrow of patients with MDS and healthy donors, then expanded in vitro. The expression of transcription factor gene RUNX2, Osterix and osteogenic differentiation markers (ALP, BSP, OPN, OCN) were measured by real-time PCR, the alkaline phosphatase(ALP) activity was assessed at 3, 7, 10 days after osteogenic differentiation. Mineralization analysis was performed at day 21 of osteogenic induction.</p><p><b>RESULTS</b>The expression level of RUNX2 and Osterix were significantly decreased in BMMSC from lower-risk MDS patients compared with normal controls (P<0.05). After osteogenic induction, low-risk MDS showed lower alkaline phosphatase activity at day 3 (P<0.05), less intense alizarin red S staining at day 21 (P<0.05), and lower gene expression of osteogenic differentiation markers (P<0.05), however, these expressions in higher-risk MDS were normal.</p><p><b>CONCLUTION</b>BMMSC from low-risk MDS have abnormalities in osteogenic differentiation, it may contribute to the ineffective hamatopoiesis of MDS.</p>

mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients / 中国实验血液学杂志

This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P < 0.05). According to WHO criteria, the mRNA expression of Delta-like-1 in RA/RAS, RCMD and RAEB groups were significantly higher than that in normal controls (P < 0.05), the mRNA expression of Jagged-1 in RAEB group was also significantly higher than that in normal controls (P < 0.05). The mRNA expression of Delta-like-1 was significantly correlated with the proportion of blasts in the bone marrow of MDS patients (r = 0.502, P < 0.05). The expression levels of Delta-like-1 and Jagged-1 in MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P < 0.05). The mRNA expression of Delta-like-1 in higher risk group according to International Prognostic Scoring System was significantly higher than that in lower risk group (P < 0.05), there was no significant difference in Jagged-1 expression levels between higher risk group and lower risk group (P > 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.

Significance of chromosome 7 abnormalities in myeloid malignancies / 中国实验血液学杂志

Chromosome 7 abnormalities are the most common cytogenetic alterations found in myeloid malignancies. Myeloid malignancies exhibiting monosomy 7/del (7q) have been confirmed to associate with high susceptibility to infections, poor response to chemotherapy, and short survival time, so speculating that chromosome 7 has important tumor suppressor genes. Commonly deleted segments (such as 7q22) of chromosome 7 have been identified by FISH and other technologies. Genes (EZH2, MLL5, DOCK4, SAMD9L/SAMD9) located in commonly deleted segments of 7q have been cloned and characterized along with the advance of molecular biology.This review summaries the current advancement about myeloid malignancies associated with monosomy7/del(7q).

Large granular lymphocyte leukemia / 中国实验血液学杂志

Large granular lymphocytic (LGL) leukaemia is an uncommon clonal lymphoproliferative disorder. The WHO classification recognizes three distinct disorders of LGLs: T-cell large granular lymphocytic leukaemia (T-LGL), chronic lymphoproliferative disorders of NK-cells (CLPD-NK) and aggressive NK-cell leukaemia. Despite the different origin of cells, there is considerable overlap between T-LGL and CLPD-NK in terms of clinical presentation and treatment. Majority of these patients are asymptomatic and may not need treatment. When significant cytopenias occur, the application of immunosuppressive therapy often should be considered. In contrast, aggressive NK cell leukemia and the rare CD56(+) aggressive T-LGL leukemia have a fulminant clinical course and an earlier age of onset, therefore, more intensive combination chemotherapy is required, followed by allogeneic hematopoietic stem cell transplantation. However, these diseases are relatively rare, there are few clinical trials to guide management. In this review, the pathogenesis, diagnosis, treatment and prognosis of this leukemia are summarized and discussed.

Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients / 中国实验血液学杂志

This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPO<1 000 U/L MDS patients were given rEPO therapy. The results showed that the level of EPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P < 0.05). Obviously, the level of EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviate EPO resistance in patients wtih anemic MDS, decrease the pathological level of EPO, enhance Hb levels and reduce the dependency on blood transfusion.

Roles of osteoblasts in hematopoietic stem cell niche and relationship between osteoblasts and hematopoietic diseases / 中国实验血液学杂志

Hemopoietic stem cells(HSCs) are regulated by two niches: osteoblastic niche and vascular niche. Osteoblasts are the critical constitutive regulators of the osteoblastic niche. The significance of osteoblasts for hematopoietic disease has not escaped attention. This review attempts to capture the discoveries of the last few years regarding the role of osteoblasts in hematopoietic stem cell niche and relationship between osteoblasts and hematopoietic diseases.

Recent advances on the prognostic value of immunophenotyping in multiple myeloma by flow cytometry / 中国实验血液学杂志

Clinical application of flow cytometry in multiple myeloma (MM) can be found in various dimensions, such as in differential diagnosis of malignant plasma cell disorder from reactive plasmacytosis, identification of the progression risk in MM, and in the detection of minimal residual disease. Flow cytometry-based clonality assessment with immuno-phenotyping encourages and enables the most stringent method of diagnosis and follow-up. The objective of this review is to summarize the recent information of the malignant plasma cell phenotypic profile of MM. The most comprehensive antigens, such as CD19, CD27, CD28, CD45, CD56 and CD117, play a significant role in the characterization of normal and malignant plasma cells. This review also focuses on the association of malignant phenotypic markers with chromosomal aberrations that identify the specific prognostic factors in MM.

Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate phenotype, cell differentiation and cytogenetic properties of bone marrow (BM) mesenchymal stem cells (MSC) separated from the myelodysplastic syndrome (MDS) patients. And to analyze cytogenetic aberration of MSC derived from MDS (MDS-MSC) and its mechanism in pathogenesis of MDS.</p><p><b>METHODS</b>Adherent MSC from both myelodysplastic (n = 22) and normal (n = 7) marrow were obtained by a stromal culture procedure. Morphological features were observed by optical microscope. The cell-surface antigens were performed by flow cytometer(FCM). Adipogenic and osteogenic differentiation potential of MSC were identified under specific induction conditions. Standard cytogenetic analysis of both hematopoietic cells and MSC were performed by trypsin-Giemsa (GTG) banding. The karyotype analysis DNA content was determined by FCM to verify the results.</p><p><b>RESULTS</b>The morphology of MDS-MSC was typical slender spindle-shaped cells, MSC obtained from MDS patients had a MSC immunophenotype, lacked the expression of hematopoietic antigens-CD34, CD45 and expressed MSC markers, such as CD73, CD90, and CD105. MDS-MSC layers showed the capability to differentiate towards adipocytes, chondrocytes and osteoblasts. Cytogenetic aberrations were observed in MSC from 14 (64%) MDS patients, usually involve the loss of chromosomal material (92%), and the clonal loss (7 cases, 50%). Two cases of structural aberrations were also detected. Abnormal karyotypes in MSC were still more frequently identified in abnormal hematopoietic cells group (12 out of 13, 92% vs 3 out of 9, 33%, P < 0.05). There were not exactly the same type of chromosomal aberrations between hematopoietic cells and MSC, but different type of the aberrations in the same chromosome were involved.</p><p><b>CONCLUSION</b>MDS-MSC retains the phenotyping characteristics and differentiated function of normal MSC, but has different type of chromosomal abnormalities. A high proportion of loss of chromosomal may be a marker of chromosomal instability of MDS-MSC. Detection of abnormalities in MDS-MSC suggests enhanced genetic susceptibility of these cells in MDS. This may indicate potential involvement of MSC in the pathophysiology of MDS.</p>

Current understanding of iron overload hazard in patients with myelodysplastic syndrome / 中国实验血液学杂志

Patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop into transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Thereby our current understanding of the effects of transfusion dependency and iron overload in MDS are discussed. Particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron and oxidative stress in iron overload, decreased life expectancy and increased risk of leukemic transformation in MDS patients with iron overload.

Function of peripheral blood Th17 cells in patients with multiple myeloma / 中国实验血液学杂志

This study was aimed to investigate the effects of peripheral blood Th17 cells and their secreting IL-17, IL-21 in the occurrence and development of multiple myeloma (MM). A total of 55 patients with MM were divided into non-remission group (group A , n = 30), remission group (group B, n = 25); healthy volunteers were used as control group (group C , n = 30). The concentration of IL-17, IL-21 and IL-6 in the peripheral blood mononuclear cell (PBMNC) culture supernatant were determined with ELISA. The ratio of Th7 cells in PBMNC was determined by flow cytometry. The results showed that IL-17, IL-21 levels and ratio of Th17 cells in group A were much higher than those in group B and C (P < 0.05), IL-17, IL-21 and the ratio of Th17 cells between group B and group C were not significantly different (P > 0.05); IL-17 level in non-remission MM group positively correlated with IL-6 level (r = 0.782, P < 0.05), IL-21 level in non-remission MM group positively correlated with IL-6 level (r = 0.778, P < 0.05). It is concluded that Th17 cells as a initiating factor may be involved in the immune pathogenesis of MM patients, promoting the progress of the disease.

p15(INK4B) methylation on prognosis and response to decitabine in patients with MDS / 中华血液学杂志

<p><b>OBJECTIVE</b>To detect p15(INK4B) methylation levels and the kinetics of the methylation status before and after decitabine to explore its influences on prognosis and response to decitabine in myelodysplastic syndromes (MDS) patients.</p><p><b>METHODS</b>We examined 261 MDS patients (143 male and 118 female) with the median age of 52 years (32-78). Of them, 172 cases were low-risk group (low-risk 104 cases, intermediate-1 68 cases), 89 cases high-risk group (intermediate-2 52 cases, high risk 37 cases). Collections of bone marrow mononuclear cells of MDS patients and extracted the genomic DNA, the methylation status of p15(INK4B) was detected by methylation-specific PCR (MSP) method. Survival analysis was conducted according to the level of p15(INK4B) methylation in the cohort of patients. The kinetics of the methylation levels of p15(INK4B) in 58 MDS patients before and after 2 courses of decitabine have been assessed with the method of MSP.</p><p><b>RESULTS</b>The methylation level of p15(INK4B) in low-risk group patients was significantly lower than that in high-risk group (117.22 vs 157.63, P<0.05 ). The expected 2-year survival rate of p15(INK4B) methylation positive patients was lower than that of negative ones (91.8% vs 69.8%, P<0.05); the expected 2-year survival rate of p15(INK4B) methylation positive patients was shorter than that of negative ones in low-risk group（78.2% vs 92.0%, P<0.05）, meanwhile there was no significant difference in terms of expected 2-year survival rate and median expected survival between p15(INK4B) methylation positive and negative patients in high-risk group [35.6% vs 38.5%, (17.0±9.3) month vs (18.0±5.7) month, P>0.05]. Multivariate analysis showed p15(INK4B) methylation degree was an independent prognostic factor for overall survival. No statistical difference of overall response (OR) rates were found between p15(INK4B) methylation positive patients and negative patients before decitabine（65.9% vs 76.5%, P>0.05）, and complete remission (CR) rates between these two groups also showed no statistical difference（22.0% vs 29.4%, P>0.05）. p15(INK4B) methylation levels had no obvious change before and after treatment in decitabine responders（P>0.05）.</p><p><b>CONCLUSION</b>The survival of newly diagnosed MDS patients with positive p15(INK4B) methylation was comparatively shorter, but p15(INK4B) methylation had no influence on response to decitabine.</p>