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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00873574
First received: March 31, 2009
Last updated: March 7, 2013
Last verified: March 2013

March 31, 2009
March 7, 2013
September 2008
May 2011   (final data collection date for primary outcome measure)
Allelic frequency comparison between the 2 cohorts [ Time Frame: At the inclusion visit ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00873574 on ClinicalTrials.gov Archive Site
Undescribed gene mutations. [ Time Frame: At the inclusion visit ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
JAK-STAT Signalling Pathway in Familial Myeloproliferative Disorders
Molecular Study of Factors Involved in JAK-STAT Signalling Pathway in Familial Myeloproliferative Disorders

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

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.

Observational
Observational Model: Case Control
Time Perspective: Cross-Sectional
Not Provided
Retention:   Samples With DNA
Description:

Peripheral blood samples (35 ml) and buccal swabs

Non-Probability Sample

Population of familial patients with MPD and controls

Myeloproliferative Disorders
Biological: Blood samples and buccal swabs
Peripheral blood samples (35 ml) and buccal swabs
Other Name: Blood samples and buccal swabs
  • 1
    2 patients with MPD for each family. One case for each family will be randomised ; the cohort will be of 120 patients.
    Intervention: Biological: Blood samples and buccal swabs
  • 2
    1 control for each family
    Intervention: Biological: Blood samples and buccal swabs
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
234
September 2012
May 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00873574
AOR 07014
No
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Principal Investigator: Albert NAJMAN, MD PhD Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP