Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsored by: |
Assistance Publique - Hôpitaux de Paris |
---|---|
Information provided by: | Assistance Publique - Hôpitaux de Paris |
ClinicalTrials.gov Identifier: | NCT00873574 |
The main goal of the study is to progress in our understanding of the molecular basis of myeloproliferative disorders of the bone marrow (polycythemia vera, essential thrombocythemia, primary myelofibrosis). The study will focus on the genes encoding factors implicated in the JAK-STAT pathway which has an essential role in these diseases
Condition | Intervention |
---|---|
Myeloproliferative Disorders |
Biological: Blood samples and buccal swabs |
Study Type: | Observational |
Study Design: | Case Control, Cross-Sectional |
Official Title: | Molecular Study of Factors Involved in JAK-STAT Signalling Pathway in Familial Myeloproliferative Disorders |
Peripheral blood samples (35 ml) and buccal swabs
Estimated Enrollment: | 120 |
Study Start Date: | September 2008 |
Estimated Study Completion Date: | September 2011 |
Estimated Primary Completion Date: | March 2011 (Final data collection date for primary outcome measure) |
Groups/Cohorts | Assigned Interventions |
---|---|
1
2 patients with MPD for each family. One case for each family will be randomised ; the cohort will be of 120 patients.
|
Biological: Blood samples and buccal swabs
Peripheral blood samples (35 ml) and buccal swabs
|
2
1 control for each family
|
Biological: Blood samples and buccal swabs
Peripheral blood samples (35 ml) and buccal swabs
|
Myeloproliferative disorders (MPD) are rare malignant diseases of the bone marrow characterized by a proliferation of differentiated blood cells during a long time and a possible transformation in an acute leukaemia. The recent identification of a recurrent activating tyrosine kinase mutation V617F in the JAK2 gene provides a breakthrough in the understanding of the molecular mechanisms of these diseases. It can't explain nevertheless the phenotypic diversity of MPD and the occurrence of familial aggregations. We have shown actually that the mutation V617F is a somatic one which is variably expressed among patients in the same family.Other somatic mutations and inherited factors, still unknown, may explain these discrepancies. JAK-STAT pathway has an essential role in non-CML MPD as was shown by the functional consequences of the V617F JAK2 mutation. Therefore, we will focus our study on the genes encoding factors implicated in this signalling pathway. Two genetic approaches will be used: 1-study of known polymorphisms (SNP) of theses genes involved in the JAK-STAT pathway; 2-search of rare mutations located in specific regions (binding domain…) of candidate genes.The study is a national multicenter research based on the national network (55 centers) that we have organized with the help of the French Society Of Hematology in 1998. We propose to include 120 families defined by the presence of at least 2 cases of non CML MPD (WHO and PVSG criteria).We have already collected 60 families (affected cases and control subject); the other 60 will be included in the next two years. In each family, only the two patients with MPD and one control will be included ( all the subjects above 18 years old). Peripheral blood samples (35ml) and buccal swabs will be collected for each subject. Hematologists and ONCOGENETICIANS will include the families, collect all the clinical and biological data and perform the collection of biological material from each subject included in the study according to approved rules.All the data will be anonymously registered on Access data base. Hematological studies will be done in the Immuno-Hematological Laboratory in Saint ANTOINE.
Genetic studies will be conducted in the Genetic Department of Saint ANTOINE Hospital now transferred to Pitié-Salpétrière Hospital in Paris. The genetic study will be based on the analysis of 120 unrelated familial SMP cases (randomised) and 120 controls. We will study 10 genes involved in the JAK-STAT pathway ( cytokine receptors, Janus kinases, regulatory factors).The genotyping of SNPs, selected from HAPMAP and CGEMS databases will be performed by quantitative PCR. We plan to analyse 50 SNPs per subject i.e. 24000 genotypes (duplicate points). The analysis will be based on the allelic frequency comparison in the two groups using a bilateral paired t-test; 120 pairs of subjects (case control) allow to detect a 0.6 deviation standard of allelic frequency between cases and controls (alpha = 5%, beta = 10%). The search for rare mutations will be done by genomic sequencing of particular regions in candidates genes in the 120 affected cases.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Population of familial patients with MPD and controls
Inclusion Criteria:
Exclusion Criteria:
Contact: Albert Najman, MD, PhD | +33 1 49 28 26 23 | albert.najman@sat.aphp.fr |
Contact: Christine Bellanné-Chantelot, PhD | +33 1 42 17 79 71 | christine.bellanne-chantelot@psl.aphp.fr |
France | |
Department of Hematology, Hospital Saint Antoine | Recruiting |
Paris, France, 75012 | |
Contact: Albert Najman, MD, PhD +33 1 49 28 26 23 albert.najman@sat.aphp.fr | |
Principal Investigator: Albert Najman, MD, PhD |
Principal Investigator: | Albert NAJMAN, MD PhD | Assistance Publique - Hôpitaux de Paris |
Responsible Party: | Department Clinical Research of Developpement ( Therese Ngoue ) |
Study ID Numbers: | AOR 07014 |
Study First Received: | March 31, 2009 |
Last Updated: | March 31, 2009 |
ClinicalTrials.gov Identifier: | NCT00873574 History of Changes |
Health Authority: | France: Ministry of Health |
Familial myeloproliferative disorders JAK-STAT V617 JAK2 |
Hematologic Diseases Myeloproliferative Disorders Bone Marrow Diseases |
Pathologic Processes Disease Hematologic Diseases Myeloproliferative Disorders Bone Marrow Diseases |