Prognostic Significance of WT1 mRNA and Anti-WT1 Antibody Levels in Peripheral Blood in Patients with Myelodysplastic Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3821-3821
Author(s):  
Hideto Tamura ◽  
Kazuo Dan ◽  
Norio Yokose ◽  
Rika Iwakiri ◽  
Masatsugu Ohta ◽  
...  
Keyword(s):  
Immune Response ◽  
Mrna Expression ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Refractory Anemia ◽  
Mrna Levels ◽  
Disease Subtype

Abstract Abstract 3821 Poster Board III-757 (INTRODUCTION) The Wilms tumor gene (WT1) message is overexpressed in tumor cells from various solid cancers as well as hematologic malignancies including myelodysplastic syndromes (MDS). We reported previously that WT1 mRNA expression in peripheral blood mononuclear cells (PBMCs) as well as bone marrow (BM) cells increased with the aggressiveness of MDS disease subtype as defined by the French-American-British (FAB) classification and that a humoral immune response, IgG- or IgM-type anti-WT1 antibody (Ab) expression, was detected in sera from most MDS patients. In this study, we investigated whether WT1 mRNA expression and anti-WT1 Ab titers in PB were associated with prognosis in MDS patients by examining their long-term follow-up data. (METHODS AND RESULTS) (1) WT1 mRNA expression in PBMCs was examined in 80 patients: 35 with refractory anemia (RA); 5 with RA with ringed sideroblasts (RARS); 24 with RA with excess blasts (RAEB); 5 with RAEB in transformation (RAEB-t); and 11 with acute myeloid leukemia transformed from MDS (AML-MDS). Levels of WT1 mRNA expression were assessed using the real-time quantitative polymerase chain reaction [Tamaki H, et al, Leukemia 1999]. WT1 mRNA levels increased with the aggressiveness of disease subtype (mean: RA, 220.9; RARS, 129.4; RAEB, 5,554.3; RAEB-t, 14,284.0; AML-MDS, 56,272.7 copies/μg) and with the aggressiveness of the International Prognostic Scoring System (IPSS) category (mean: low, 114.5; intermediate-1, 360.8; intermediate-2, 12,041.6; high, 7,357.9 copies/μg) in these patients. (2) IgG- and IgM-type anti-WT1 Ab titers were determined using the dot-blot assay [Elisseeva OA, Blood 2002] in sera from 45 of the 80 patients: 15 RA; 3 RARS; 18 RAEB; 3 RAEB-t; and 6 AML-MDS. IgM and IgG WT1 Abs were detected in 31 (79.5%) and 34 (87.2%) MDS patients, and 5 (83.3%) and 6 (100%) AML-MDS patients, respectively. WT1 Abs levels were not correlated with FAB subtype, IPSS, or WT1 mRNA expression in PBMCs. (3) When patients were divided into three groups based on the WT1 mRNA level (fewer than 100 copies/μg, 100 to 10,000 copies/μg, and more than 10,000 copies/μg), their survival rates differed significantly (P = 0.0186): survival was worse in those with increased WT1 mRNA levels. Specifically, a high WT1 mRNA level was a strong predictor of rapid AML transformation even if adjusted by the IPSS (P = 0.0005). Furthermore, patients with high levels of either IgM or IgG WT1 Abs had significantly better survival compared with those whose IgM and IgG WT1 Abs values were both low (P = 0.0007) even when adjusted by the IPSS (P = 0.0019). (CONCLUSIONS) This study showed for the first time that high WT1 mRNA expression and high WT1 Ab titers in PB affected the prognosis of MDS patients negatively and positively, respectively, suggesting that an optimal immune response against WT1 may beneficial. Recently, clinical trials of WT1 peptide-based immunotherapy have been conducted for various malignancies including MDS. Our data presented here may provide a rationale for anti-WT1 immunotherapy in MDS. Disclosures: No relevant conflicts of interest to declare.

Expression of WT-1 mRNA in Peripheral Blood from Myelodysplastic Syndromes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3637-3637
Author(s):  
Hideto Tamura ◽  
Kazuo Dan ◽  
Norio Yokose ◽  
Rika Iwakiri ◽  
Masatsugu Ohta ◽  
...  
Keyword(s):  
High Risk ◽  
Mrna Expression ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Refractory Anemia ◽  
Mrna Levels ◽  
Cell Counts ◽  
Fab Classification

Abstract (INTRODUCTION) The Wilms’ tumor gene WT-1 is overexpressed in various types of solid tumor as well as in hematologic malignancies, i.e., acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic myeloid leukemia, and myelodysplastic syndromes (MDS). It was reported that WT-1 overexpression in peripheral blood (PB) and bone marrow (BM) is useful for the monitoring of minimal residual disease and early detection of relapse in AML. MDS are clonal hematologic stem cell disorders characterized by cytopenias and a risk of progression to acute leukemia. It is important for decisions on treatment strategy to assess disease progression and predict the prognosis in MDS. The aim of this study was to investigate the clinical significance of WT-1 mRNA expression in PB obtained from patients with MDS. (METHODS AND RESULTS) PB was obtained from 92 patients with MDS or leukemia transformed from MDS (AL-MDS): 40 refractory anemia (RA), 5 RA with ringed sideroblasts (RARS), 27 RA with excess blasts (RAEB), 5 RAEB in transformation (RAEB-t), and 15 AL-MDS cases in the FAB classification (RA 27, RARS 5, refractory cytopenia with multilineage dysplasia 12, RAEB-1 13, RAEB-2 14, 5q- 1, and AL-MDS 20 cases in the WHO classification). RNA was isolated from PB mononuclear cells (PBMCs) and converted into cDNA. The levels of WT-1 mRNA expression were assessed using the real-time quantitative polymerase chain reaction. We analyzed whether the level of WT-1 mRNA expression in PBMCs was associated with MDS subtype in the FAB classification, clinical characteristics (hemoglobin value, white blood cell counts, neutrophil counts, lymphocyte counts, chromosomal abnormality, number of cytopenias, blast percentages in BM, lactate dehydrogenase values, C-reactive protein values), International Prognostic Scoring System (IPSS) score, survival, and time to leukemia transformation. High expression of WT-1 mRNA, which was defined as more than 50 copies/μg mRNA according to the results of normals, was observed in 42.5%, 40.0%, 85.2%, 80.0%, and 100% of RA, RARS, RAEB, RAEB-t, and AL-MDS patients, respectively. The WT-1 mRNA levels increased with the aggressiveness of disease subtype and IPSS. FAB subtypes included RARS (mean ± SD, 129 ± 111 copies/μg), RA (220 ± 134), RAEB (5554 ± 2593), RAEB-t (14284 ± 9056), and AL-MDS (51591 ± 30309). IPSS score were divided into low/intermediate-1 risk (316 ± 136) and intermediate-2/high risk (7901 ± 3035) (P < 0.05 for RA vs RAEB, RAEB-t or AL-MDS; RAEB vs AL-MDS; and low/intermediate-1 vs intermediate-2/high risk). Furthermore, the WT-1 mRNA level was inversely correlated with the neutrophil percentage in PB and positively correlated with the blast percentage in both PB and BM. Among RA patients, those with favorable cytogenetics had lower WT-1 mRNA values compared with other patients (P < 0.05). When patients were divided into three groups based on the log value of WT-1 mRNA (<2, 2–4, and >=4), the survival times of those groups were 73.1, 55.6, and 15.3 months, respectively (P < 0.005). (CONCLUSIONS) Higher quantitative expression of WT-1 mRNA in PBMCs is associated with aggressive disease behavior in MDS patients. This may justify anti-WT-1 immunotherapy under investigation for MDS treatment (PNAS2004;101:13885–13890).

scholarly journals Prognostic significance of Wilms tumor 1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes

2016 ◽  
Vol 17 (1) ◽  
pp. 21-32 ◽  
Author(s):  
Sumiko Kobayashi ◽  
Yasunori Ueda ◽  
Yasuhito Nannya ◽  
Hirohiko Shibayama ◽  
Hideto Tamura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Wilms Tumor ◽  
Prognostic Significance ◽  
Expression Levels ◽  
Wilms Tumor 1 ◽  
Mrna Expression Levels

The Recent Thymic Output Function Might Relate with BCR-ABL mRNA Level in Patients with CML.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4768-4768
Author(s):  
Suxia Geng ◽  
Xin Du ◽  
Jianyu Weng ◽  
Lijian Yang ◽  
Shaohua Chen ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Fusion Gene ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Myelogenous Leukemia ◽  
Quantitative Detection ◽  
Mrna Levels ◽  
Output Function ◽  
Post Transplantation ◽  
Thymic Output

Abstract Objective In order to analyze the relationship between the content of T-cell receptor excision DNA circles (TRECs) and BCR-ABL mRNA levels, evaluating the prognostic significance of thymic recent output function monitoring in patients with chronic myelogenous leukemia (CML). Methods Quantitative detection of TRECs and BCR-ABL fusion gene transcripts in peripheral blood from 15 CML patients were preformed using real-time PCR technique. And the TREC-number was related to the number of T-cells by determination of the number of CD3-positive cells. The change of BCR-ABL level in 6 CML patients was followed-up for two years. Results There was no significant correlation between TRECs and BCR-ABL mRNA in peripheral blood from CML patients at the first diagnose. Patients who had higher TRECs at diagnosis had a larger reduction of BCR-ABL level after 2 years of follow-up. While in 2 patients who underwent haemopoietic stem cell transplantation(HSCT), BCR-ABL in one patient with higher pre-transplantation TRECs value became undetectable with three consecutive detections during the first year post transplantation, but low level of BCR-ABL could be identified in the other patient. Conclusion High thymic output function in CML patients could be helpful for anti-residual CML cells.

scholarly journals Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia

2019 ◽  
Vol 97 (6) ◽  
pp. 562-569 ◽  
Author(s):  
Anthony Cannavicci ◽  
Qiuwang Zhang ◽  
Si-Cheng Dai ◽  
Marie E. Faughnan ◽  
Michael J.B. Kutryk
Keyword(s):  
Growth Factor ◽  
Peripheral Blood ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Clinical Manifestations ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Peripheral Blood Mononuclear ◽  
Micro Rnas

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder inherited in an autosomal dominant manner. Patients with HHT can develop vascular dysplasias called telangiectasias and arteriovenous malformations (AVMs). Our objective was to profile and characterize micro-RNAs (miRNAs), short noncoding RNAs that regulate gene expression posttranscriptionally, in HHT patient-derived peripheral blood mononuclear cells (PBMCs). PBMCs, comprised mostly of lymphocytes and monocytes, have been reported to be dysfunctional in HHT. A total of 40 clinically confirmed HHT patients and 22 controls were enrolled in this study. PBMCs were isolated from 16 mL of peripheral blood and purified for total RNA. MiRNA expression profiling was conducted with a human miRNA array analysis. Select dysregulated miRNAs and miRNA targets were validated with reverse transcription–quantitative polymerase chain reaction. Of the 377 miRNAs screened, 41 dysregulated miRNAs were identified. Both miR-28-5p and miR-361-3p, known to target insulin-like growth factor 1 (IGF1), a potent angiogenic growth factor, were found to be significantly downregulated in HHT patients. Consequently, IGF1 mRNA levels were found to be significantly elevated. Our research successfully identified miRNA dysregulation and elevated IGF1 mRNA levels in PBMCs from HHT patients. This novel discovery represents a potential pathogenic mechanism that could be targeted to alleviate clinical manifestations of HHT.

scholarly journals Dose-dependent immune response in milk cells and mammary tissue after intramammary administration of lipopolysaccharide in dairy cows

2008 ◽  
Vol 52 (No. 6) ◽  
pp. 231-244 ◽  
Author(s):  
C. Werner-Misof ◽  
M.W. Pfaffl ◽  
R.M. Bruckmaier
Keyword(s):  
Immune Response ◽  
Mrna Expression ◽  
Real Time ◽  
Polymorphonuclear Neutrophils ◽  
Mammary Tissue ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Lps Challenge ◽  
Cell Counts ◽  
Cox 2

The immune response in milk cells and the status of mammary tight junctions (TJ) in response to intramammary (IM) infusion of different doses of <i>Escherichia col</i>i lipopolysaccharide (LPS) was investigated. <i>Experiment I</i>: Seven German Braunvieh cows were IM infused into one quarter with 1 &mu;g (LPS-1) and 3 &mu;g (LPS-3) of LPS, respectively, and the contralateral control quarter with saline (9 g/l; C). Milk samples were taken immediately before and 12, 24, 36, 48, 60, 84 and 108 h after infusion and analysed for somatic cell counts (SCC), lactose, sodium (Na) and chloride (Cl) ions, and electrical conductivity (EC). Milk cell mRNA expression of various inflammatory factors was quantified by real-time RT-PCR. Blood samples were taken immediately after milking for the analysis of leukocytes (WBC), polymorphonuclear neutrophils (PMN), Na and Cl. Milk SCC, lactose, Na, Cl and EC did not differ significantly between LPS-1 and C quarters after the challenge. In LPS-3 quarters SCC levels increased within the first 12 h, reached peak levels between 12 and 36 h (<i>P</i> &le; 0.001) and decreased (<i>P</i> &le; 0.05) thereafter to reach baseline at 108 hours. Lactose in LPS-3 quarters decreased (<i>P</i> &le; 0.05) to a minimum at 24 h and increased slightly thereafter while EC, Na, and Cl increased transiently in response to LPS-3. WBC and PMN levels in both groups decreased numerically within 24 h after LPS administration. In LPS-1, WBC at 24, 48 and 108 h were significantly lower whereas in LPS-3 they were significantly higher than at time 0. TNF&alpha;-mRNA expression in both groups did not change in response to IM LPS-challenge. IL-1&beta;-mRNA expression at 12, 24 and 36 h in LPS-1 quarters increased significantly as compared to time 0. In LPS-3 quarters the mRNA expression values of all tested ILs increased significantly as compared to time 0 within 12 h after LPS-challenge. IL-1&beta;-mRNA expression decreased (<i>P</i> &le; 0.05) at 48 and 84 h in LPS quarters. IL-8 mRNA was significantly decreased at 84 h after challenge in LPS-3 quarters. COX-2-mRNA expression in LPS-1 quarters decreased significantly as compared to time 0 at 48, 84 and 108 h, with a minimum at 84 h (<i>P</i> &le; 0.05). In LPS-3 quarters COX-2-mRNA levels increased (<i>P</i> &le; 0.05) within 48 h after the LPS-challenge. <i>Experiment II</i>: Six cows (5 German Braunvieh, 1 Brown Swiss) were injected in one quarter with 100 &mu;g LPS and in the contralateral quarter with saline (9 g/l; C). Mammary biopsy samples of both quarters were taken immediately before and at 3, 6, 9 and 12 h after infusion and mRNA expression of TJ proteins occludin (OCLN) and zonula occludens (ZO-) 1, 2 and 3 were quantified by real-time RT-PCR. OCLN-mRNA expression did not change in response to the IM infusion while that of ZO-1, ZO-2 and ZO-3 decreased significantly within six hours. In conclusion, a dose of 1 &mu;g LPS did not initiate a immune response in the mammary gland. Furthermore the dose of 100 &mu;g of LPS enhanced TJ permeability by reducing TJ plaque proteins density.

scholarly journals Obesity May Provide Pro-ILC3 Development Inflammatory Environment in Asthmatic Children

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yumin Wu ◽  
Jiawei Yue ◽  
Juncheng Wu ◽  
Wei Zhou ◽  
Dapeng Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Messenger Rna ◽  
Mrna Level ◽  
Asthma Severity ◽  
Lymphoid Cells ◽  
Mrna Levels ◽  
Asthmatic Children ◽  
Prevalence Of Obesity ◽  
Elevated Frequency ◽  
Relative Mrna Expression

The prevalence of obesity in children has dramatically increased in the last few decades, and obesity has also emerged as an important risk factor for asthma. Innate mechanisms have been shown to be involved in both diseases, particularly through the recently described innate lymphoid cells (ILCs), in which ILC3s have been linked to obesity both in human and in murine models. The aim of this study was to explore whether being overweight in asthmatic children was associated with elevated circulating ILC3 or elevated messenger RNA (mRNA) levels of RORC, IL-17A, and IL-22. Our results showed significantly elevated ILC3 frequencies in overweight asthmatic children compared with nonoverweight controls based on the detection of Lin+CD127+IL-23R+ cells by flow cytometry. Moreover, elevated ILC3 frequencies positively correlated with the mRNA expression of RORC which has been identified as a transcription factor of ILC3s. The relative mRNA expression level of IL-17A was also upregulated in overweight compared to nonoverweight children, as was the relative mRNA level of IL-22. However, there were no correlations between ILC3 frequencies or the expressions of RORC, IL-17A, and IL-22 and asthma severity. These results suggested that childhood obesity is an independent factor that is associated with an elevated frequency of circulating ILC3s and higher expressions of RORC, IL-22, and IL-17A.

Prognostic Impact of the Detection of the WT1 Gene mRNA with Peripheral Blood in Adult Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3289-3289
Author(s):  
Shuichi Miyawaki ◽  
Nahoko Hatsumi ◽  
Toshiharu Tamaki ◽  
Tomoki Naoe ◽  
Keiya Ozawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Consolidation Therapy

Abstract Background: Approximately 70–80% of all newly diagnosed patients with adult AML achieve a complete remission (CR). However, only about one third of those pts remain free of disease for more than 5 years. It is therefore important to predict which pts are most likely to suffer a relapse and thus perform alternative treatments such as stem cell transplantation in order to improve the prognosis of AML. We evaluated the impact of the detection of Wilms’ tumor gene1 (WT1) mRNA in the peripheral blood on the prognosis of AML pts. Patients and Methods: From June 1, 2001 to October 30, 2003 a study was performed on 191 pts with AML which evaluated the clinical usefulness of a WT1 mRNA assay kit for the early detection of relapse in AML pts (submitted in Rinsho Ketsueki). From these 191 pts, we selected the subjects for this study. All selected subjects achieved a complete remission, and also had their WT1 expression analyzed after consolidation therapy. The pts were excluded if they had received a stem cell transplantation before relapse. The WT1 mRNA levels were determined using the WT1 mRNA assay kit (Otsuka Pharmaceutical Co. Ltd) in accordance with the standard operating procedures using peripheral blood. The lower limit of detection was 50 copy/μgRNA. Therefore, less than 50 copy/μgRNA was judged as negative. All induction, consolidation and maintenance therapies were performed according to institutional standards. Results: Of 118 pts who achieved a complete remission, 50 pts (median age: 56 yrs 22–86) were evaluable. Their median WT1 mRNA levels before induction therapy was 48327 copy/μgRNA (137–329185). The WT1 mRNA levels at diagnosis did not correlate with either the relapse rate, DFS or OS, respectively. After CR, the WT1 mRNA level ranged from &lt;50 copy/μg to 30732 copy/μgRNA. Thirty-four (69.4%) pts were positive and 15 pts (30.6%) were negative for the WT1 mRNA. The relapse rate of the positive pts and of the negative pts was 73.5% and 40.0% (P=0.0248 sensitivity=80.6 % specificity=50.0%), respectively. The OS rate at 3 years was 53.1% in the positive pts and 79.0% in the negative pts (P=0.1227), respectively. The DFS rate at 3 years was 30.0% in the positive pts and 60.0 % in the negative pts (P=0.0906), respectively. After consolidation therapy, the WT1 mRNA level ranged from &lt;50 copy/μgRNA to 49174 copy/μgRNA. The WT1 positive pts numbered only 15 pts (32.6%) and the negative pts numbered 31 (67.4%). The relapse rate of the positive pts and the negative pts was 80.0% and 54.8% (P=0.0974), respectively. The OS of rate at 3 years was 42.8% in the positive pts and 69.8% in the negative pts (P=0.0381), respectively. The DFS rate at 3 years was 20.0% in the positive pts and 50.0% in the negative pts (P=0.0116). The rate of relapse within 1 year was 73.3% in the positive pts and only 33.3% in the negative pts (P= 0.0116). Conclusion: This study shows that the detection of the WT1 mRNA in the peripheral blood after treatment closely correlated with the prognosis in AML.

Thrombocytosis as a Presenting Feature in Myelodysplastic Syndromes (MDS) in Adults - 40 Year Experience from a Single Institution in the USA.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4831-4831
Author(s):  
Dhatri Kodali ◽  
Hector Mesa ◽  
Ajay Rawal ◽  
Pankaj Gupta
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Clinical Course ◽  
Refractory Anemia ◽  
Risk Category ◽  
Platelet Counts ◽  
Hydroxyurea Treatment

Abstract Thrombocytosis at presentation is uncommon in the myelodysplastic syndromes (MDS), and its influence on the clinical course of the disease and on prognosis is uncertain. To determine the clinical course and long-term outcomes of patients (pts) with thrombocytosis at initial diagnosis of MDS, we conducted a retrospective analysis of 503 pts diagnosed with MDS between Jan 1966 and July 2006 at the Minneapolis VA Medical Center. Original bone marrow and peripheral blood slides and reports were reviewed with a hematopathologist (H.M.) in all pts with high platelet counts (&gt; 400 × 103/μL) and evidence of dysplasia. Clinico-pathological correlation was obtained by chart review. Patients with inadequate data, secondary causes of thrombocytosis, transient thrombocytosis, and those without evidence of dysplasia were excluded. Of 503 pts, 41 (8.2%) were found to have thrombocytosis at presentation. Their median age was 74 years. The spleen was enlarged (by imaging) in 6 pts. Peripheral blood counts (mean; range) at diagnosis were: hemoglobin (10.9 g/dL; 7.4 – 17.1), absolute neutrophils (7.9 × 103/μL; 0.8 – 30.7) and platelets (627 × 103/μL; 402 – 1231). The cases were re-classified according to the WHO classification of myeloid disorders as follows: chronic myelomonocytic leukemia-1 (CMML-1) = 17 (41%), refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T) = 13 (32%) and others = 11 (27%; including 2 pts each with RA, MDS/myeloproliferative disorder-unclassified [MDS/MPD-U] and 5q- syndrome, and 1 pt each with RA with excess blasts [RAEB-1], therapy related MDS [tMDS], refractory cytopenia with multilineage dysplasia [RCMD], MDS-U and atypical chronic myeloid leukemia [Aty CML]). Bone marrow fibrosis was increased in 3 pts with CMML-1 and 1 with RARS-T, and was normal or only focally increased in all other pts. The IPSS risk category was Low in 15 pts, Int-1 in 3 pts and Int-2 in 2 pts. Cytogenetic data was not available in the other pts. Jak-2 mutation analysis was positive in 2 pts with RARS-T, negative in 1 pt each with RARS-T and MDS/MPD-U, and is pending in others. On follow-up, 2 pts with CMML-1 and 1 pt with Aty CML transformed to acute myeloid leukemia (AML) and both pts with 5q- syndrome transformed to CMML-2. Two pts with RARS-T progressed to RAEB-2 and 1 pt with CMML-1 progressed to CMML-2. One pt with CMML-1 developed marked myelofibrosis. Marked thrombocytosis required hydroxyurea treatment in 5 pts. One MDS-U pt received 5-azacytidine. Four of 41 (10%) pts experienced major bleeding events; 3 were receiving aspirin. Five pts required ongoing red cell transfusions. The median survival (MS) was 36 months in RARS-T, 60 months in CMML-1 and 27 months in others; the MS of all 41 pts was 48 months. Causes of death were AML in 3 pts, cytopenias due to MDS in 6 pts and unrelated/unknown in 21 pts. Eleven pts are currently alive. In conclusion, the majority of pts presenting with myelodysplasia and thrombocytosis fall in the MDS/MPD category of the new WHO classification (most commonly CMML or RARS-T), be older, and have low-risk features (IPSS Low or Int-1). The risks of spontaneous bleeding, transformation to AML, progression of disease or myelofibrosis are low, and the overall prognosis is relatively favorable. Platelet counts may reach levels requiring cytoreductive therapy. This study helps better understand the natural history and prognosis of this varied spectrum of MDS and overlap syndromes.

Preliminary Study on the Abnormal DNA Methylation in T Cells from the Patients with Immune Related Pancytopenia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5156-5156
Author(s):  
Zonghong Shao ◽  
Yue Ren ◽  
Rong Fu
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
Mrna Expression ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Mrna Level ◽  
Cd4 T Cell ◽  
Global Dna Methylation ◽  
Normal Controls

Abstract Objective To explore the global DNA methylation and the expression of regulatory genes for methylation in CD4 + T cells of the patients with immune related pancytopenia (IRP) and explore the role of methylation in pathogenesis of IRP. Methods Thirty IRP patients (untreated, n=15; remission, n=15) and 15 healthy donors as controls were enrolled from December 2012 to December 2013. CD4+ T cells were sorted by immunomagnetic separation. The global DNA methylation was tested with enzyme-linked immunosorbent assay (ELISA). The mRNA levels of DNA methylation-related regulating genes, DNA methyltransferases (DNMTs) and methylated CpG binding proteins (MBDs), were measured by real-time quantitative polymerase chain reaction (RT-PCR). Results The level of global DNA methylation in peripheral blood CD4+ T cells of untreated IRP patients (3.525%±2.046%)and remission patients (4.790%±1.471%) were significantly lower than that of normal controls (10.101%±3.449%) respectively (both P<0.05). DNMT3b mRNA level of untreated IRP patients (1.332±0.785) was significantly lower than that of normal controls (2.077±1.059) in CD4+T cells (P<0.05). The mRNA expression of MBD2 was significantly higher in CD4+ T cells from untreated and remission IRP patients (2.999±1.601, 2.055±1.576) than that in controls (0.581±0.247) (both P<0.05). The MBD4 mRNA level was significantly higher in CD4+ T cells from untreated IRP patients (2.736±2.719) compared to that in normal controls (1.167±1.006) (p<0.05). DNMT3b mRNA expression and CD4+ T cell DNA methylation to be positive correlated within IRP patients (r=0.569, p<0.01). The MBD2 mRNA expression negatively correlated with CD4+ T cell DNA methylation and the ratio of Th1/Th2 (r=-0.763, p<0.001; r = -0.652, p<0.05). The global methylation of CD4+ T cells negatively related to the ratio of CD5+ B cells (r= -0.439, p<0.05). Conclusions The globe DNA hypomethylation and abnormal expression of DNA methylation-related enzymes in peripheral blood CD4+ T cells may be related with the pathogenesis of IRP. Disclosures No relevant conflicts of interest to declare.

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