Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

JAK-STAT Signalling Pathway in Familial Myeloproliferative Disorders (SMP)

This study has been completed.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris Identifier:
First received: March 31, 2009
Last updated: March 7, 2013
Last verified: March 2013
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: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Molecular Study of Factors Involved in JAK-STAT Signalling Pathway in Familial Myeloproliferative Disorders

Resource links provided by NLM:

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Allelic frequency comparison between the 2 cohorts [ Time Frame: At the inclusion visit ]

Secondary Outcome Measures:
  • Undescribed gene mutations. [ Time Frame: At the inclusion visit ]

Biospecimen Retention:   Samples With DNA
Peripheral blood samples (35 ml) and buccal swabs

Enrollment: 234
Study Start Date: September 2008
Study Completion Date: September 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
1 control for each family
Biological: Blood samples and buccal swabs
Peripheral blood samples (35 ml) and buccal swabs

Detailed Description:

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. The investigators 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, the investigators 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 the investigators have organized with the help of the French Society Of Hematology in 1998. The investigators propose to include 120 families defined by the presence of at least 2 cases of non CML MPD (WHO and PVSG criteria).The investigators 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 Pitie-Salpetriere Hospital in Paris. The genetic study will be based on the analysis of 120 unrelated familial SMP cases (randomised) and 120 controls. The investigators 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. The investigators plan to analyze 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   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Population of familial patients with MPD and controls

Inclusion Criteria:

  • Patients affected with polycythemia vera, essential thrombocythemia or primary myelofibrosis
  • Familial cases
  • Subjects above 18 years old
  • Non affected controls

Exclusion Criteria:

  • patients with chronic myeloid leukaemia
  • subjects under 18 years old
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00873574

Department of Hematology, Hospital Saint Antoine
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Principal Investigator: Albert NAJMAN, MD PhD Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT00873574     History of Changes
Other Study ID Numbers: AOR 07014
Study First Received: March 31, 2009
Last Updated: March 7, 2013

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Familial myeloproliferative disorders

Additional relevant MeSH terms:
Myeloproliferative Disorders
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases processed this record on May 25, 2017