Expression data from patients with Essential Thrombocythemia (ET), Polycythemia Vera (PV), Primary Myelofibrosis (PMF) (untreated)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE61629 | GEO | 2017/02/09
SECONDARY ACCESSION(S): PRJNA261707
REPOSITORIES: GEO
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Project description:Microarrays were used to assess gene expression in patients with ET, PV, and PMF before and after treatment with IFNalpha2 in a paired design.
2018-06-15 | GSE57793 | GEO
Project description:We used microarrays to assess gene expression in patients with ET, PV, and PMF compared to control subjects
2012-01-10 | GSE26049 | GEO
Project description:We used microarrays to assess gene expression in patients with ET, PV, and PMF compared to control subjects Total RNA was purified from whole blood and amplified to biotin-labeled aRNA and hybridized to microarray chips.
2012-01-10 | E-GEOD-26049 | biostudies-arrayexpress
Project description:To define the molecular abnormalities at the stem cell level in polycythemia vera (PV), we examined global gene expression in circulating CD34+ cells from 19 JAK2 V617F-positive PV patients and 6 normal individuals using Affymetrix oligonucleotide microarray technology. We observed that CD34+ cell gene expression not only differed between the PV patients and the normal controls but also between men and women PV patients. Based on these gender-specific differences in gene expression, we were able to identify 102 genes differentially regulated concordantly by both men and women, which likely represent a core set of genes whose dysregulation is involved in the pathogenesis of PV. Gene expression was verified by Q-PCR of patient CD34+ cell RNA. Using the 102 gene set and unsupervised hierarchical clustering, the 19 PV patients could be separated in two groups that differed significantly with respect to hemoglobin level, thrombosis frequency, splenomegaly, splenectomy or chemotherapy exposure, leukemic transformation and overall survival. These results were confirmed using top scoring pairs, which identified a different set of 29 genes that independently segregated the 19 patients into the same two clinical groups: those with an aggressive form of the disease (7 patients), and those with an indolent form (12 patients).
2014-08-29 | GSE47018 | GEO
Project description:To define the molecular abnormalities at the stem cell level in polycythemia vera (PV), we examined global gene expression in circulating CD34+ cells from 19 JAK2 V617F-positive PV patients and 6 normal individuals using Affymetrix oligonucleotide microarray technology. We observed that CD34+ cell gene expression not only differed between the PV patients and the normal controls but also between men and women PV patients. Based on these gender-specific differences in gene expression, we were able to identify 102 genes differentially regulated concordantly by both men and women, which likely represent a core set of genes whose dysregulation is involved in the pathogenesis of PV. Gene expression was verified by Q-PCR of patient CD34+ cell RNA. Using the 102 gene set and unsupervised hierarchical clustering, the 19 PV patients could be separated in two groups that differed significantly with respect to hemoglobin level, thrombosis frequency, splenomegaly, splenectomy or chemotherapy exposure, leukemic transformation and overall survival. These results were confirmed using top scoring pairs, which identified a different set of 29 genes that independently segregated the 19 patients into the same two clinical groups: those with an aggressive form of the disease (7 patients), and those with an indolent form (12 patients). Samples from 19 PV patients (8 men and 11 women) and 6 normal controls (3 men and 3 women) were analyzed using Affymetrix oligonucleotide microarray U133A.
2014-08-29 | E-GEOD-47018 | biostudies-arrayexpress
Project description:A global microRNA expression profile was obtained from gradient-purified granulocytes (>95% pure) collected at the time of screening and at cycle 4 of treatment Protocol #18424-256 is a Phase 2 study of the JAK1 and JAK2 inhibitor INCB01842 in patients with advanced polycythemia vera (PV) and essential thrombocythemia (ET) refractory to hydroxyurea;
2012-09-26 | GSE32194 | GEO
Project description:Background:Pegylated interferon alfa-2a (PEG-IFN-?-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-?-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients. Methods:Among 83 patients, 58 (70%, PV 25, ET 31) had evaluable BM samples. BM responses and fibrosis grading were defined according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment, and the European Consensus on grading of BM fibrosis, respectively. BM was assessed prior to enrollment, and every 6-24 months while on therapy in all patients, and after therapy discontinuation in some patients. Results:The median age of analyzed 58 patients was 52 years, and 29% were males. After a median follow-up of 84 months, 32 patients are still on study. Hematologic (HR) and molecular responses (MR) were seen in 93 and 69% patients, respectively. Twenty-nine patients (50%) had a BM response, including 13 (22%) with a complete BM response (BM-CR). Moreover, 13 patients (22%) have experienced complete resolution of bone marrow reticulin fibrosis. Patients with BM response had higher duration of HR and MR, and lower discontinuation rate. Furthermore, patients with BM-CR had a higher probability of complete MR. The median duration of BM-CR was 30 months, and 9 patients have maintained their BM-CR (69%), including five who have maintained their response after discontinuation of therapy. Despite this observation, the pattern of HR, MR and BM response, their durability and interrelation was heterogeneous. Conclusions:Our results show the ability of PEG-IFN-?-2a to induce complete BM responses in a subset of ET and PV patients, but its correlation with durable clinically relevant treatment benefit warrants further investigation. Trial registration This study is registered with ClinicalTrials.gov (NCT00452023), and is ongoing but not enrolling new patients.
| S-EPMC5679503 | biostudies-literature
Project description:MicroRNAs (miRNA) are small non-coding RNA molecules that play critical roles in cell differentiation, proliferation and apoptosis and thus regulate haematopoietic stem cells and committed progenitor cells. We analyzed expressions of miRNAs associated with hematopoietic transformation of myeloid, erythroid and megakaryocytic progenitor cells during haematopoiesis (mir155, mir181a, mir221, mir222, mir223, mir451), in patients with primary myelofibrosis (PMF) (n = 22), polycythemia vera (PV) (n = 33), essential thrombocythemia (ET) (n = 49) and in healthy controls (n = 40) by quantitate/real time polymerase chain reaction. RT-PCR testing was negative for BCR-ABL1 fusion gene in all the patients. Mir155 was expressed in higher levels in all 3 disorders (p < 0.05). Mir221 was higher especially in ET and PMF group (p < 0.05). Mir222 expression was lower in PV patients (p < 0.05) and higher in ET and PMF patients compared to control group. Mir223 expression was higher in ET and PMF group than control group (p > 0.05). Mir451 levels were lower in all three groups compared to control group (p < 0.05). There was no difference in expression levels of mir181a between groups. JAK2V617F positivity, co-morbidities, drugs, and gender did not affect miRNA expressions. This study holds promise for the future application of these molecules for differential diagnosis and as therapeutic targets in Philadelphia chromosome negative myeloproliferative neoplasms.
| S-EPMC4542760 | biostudies-literature
Project description:High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of approximately 13%. Specific diagnoses included polycythemia vera (PV; n=89), essential thrombocythemia (ET; n=57), primary myelofibrosis (PMF; n=60), post-PV MF (n=14), post-ET MF (n=7) and blast phase PV/ET/MF (n=12); the corresponding mutational frequencies were approximately 16, 5, 17, 14, 14 and 17% (P=0.50). Mutant TET2 was detected in approximately 17 and approximately 7% of JAK2V617F-positive and -negative cases, respectively (P=0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was approximately 23% in patients > or =60 years old versus approximately 4% in younger patients (P<0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (P=0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance.
| S-EPMC4654629 | biostudies-literature
Project description:PurposeFedratinib (SAR302503, TG101348) is an orally administered Janus kinase (JAK) 2-selective inhibitor that is being developed for the treatment of patients with myelofibrosis (MF). The objectives of this analysis were to develop a population pharmacokinetic (PK) model to characterize fedratinib concentration-time profiles in patients with MF, polycythemia vera (PV) and essential thrombocythemia (ET) following oral fedratinib administration; and to investigate the effects of selected covariates on fedratinib PK parameters.MethodsNonlinear mixed effects modeling was employed in developing a population PK model for fedratinib. Intensive or sparse fedratinib concentration data collected in adult subjects with MF, PV or ET from six studies were pooled, and a total of 452 subjects and 3442 plasma concentration observations were included in the final model.ResultsFedratinib PK in patients with MF/PV/ET was adequately described by a two-compartment structural PK model with first-order absorption incorporating a lag time and first-order elimination. Following oral administration, fedratinib undergoes biphasic disposition and exhibits linear, time-invariant PK at doses of 200 mg and above. Compared to MF/ET patients, PV patients had higher apparent clearance (CL/F) and apparent central volume of distribution. Creatinine clearance was a statistically significant covariate on CL/F, and patients with mild and moderate renal impairment had 10% and 37% increases in fedratinib exposure as compared to patients with normal renal function. No clinically meaningful effect on fedratinib exposure was observed regarding age, body weight, sex, race and liver function.ConclusionsThese results should serve as the basis for dose adjustment of fedratinib for special populations.
| S-EPMC6768916 | biostudies-literature