Potential Role of CD9 and Implication of Motility Process in Pathogenesis of TEL/ALM1-positive ALL Relapses (LAL TEL/ALM1 and CD9).

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Rennes University Hospital
Sponsor:
Collaborator:
Ligue contre le cancer, France
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT01282593
First received: January 24, 2011
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

Down regulation of CD9 in TEL/AML1-positive ALL is addressed in motility assays to explore its role in B-ALL pathogenesis and its potential implication in relapses (and prognosis).


Condition Intervention
Acute Lymphoblastic Leukemia (ALL)
Other: Impact of CD9 expression level on motility assays
Other: Post-transcriptional regulation of CD9

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Potential Role of CD9 and Implication of Motility Process in Pathogenesis of TEL/ALM1-positive ALL Relapses (LAL TEL/ALM1 and CD9).

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • The potential discriminating state of CD9. - To determine the functional impact of CD9 on motility assays in TEL/AML1-positive blasts - To explore the regulation of the expression of the CD9 transcript inTEL/AML1-positive blasts [ Time Frame: 3 years ] [ Designated as safety issue: No ]

    Due to the importance of the motility process in malignant cells and the role of CD9 in cell motility regulation, we considered the potential discriminating state of CD9.

    • To determine the functional impact of CD9 on motility assays in TEL/AML1-positive blasts
    • To explore the regulation of the expression of the CD9 transcript inTEL/AML1-positive blasts


Secondary Outcome Measures:
  • - Migratory potential of blasts according to CD9 expression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    - Migratory potential of blasts according to CD9 expression

  • - Adhesion properties of blasts according to CD9 expression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    - Adhesion properties of blasts according to CD9 expression

  • - Level of miRNA, that could affect CD9 transcript levels inTEL/AML1-positive blasts versus TEL/AML1-negative ones [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    - Level of miRNA, that could affect CD9 transcript levels inTEL/AML1-positive blasts versus TEL/AML1-negative ones


Estimated Enrollment: 50
Study Start Date: November 2010
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Impact of CD9 expression level on motility assays

    1) Assess of the impact of CD9 expression level on motility assays (migration and adhesion) We have initiated motility assays (fibronectin adhesion experiments and CXCL12 chemoattracted migration tests with modified Boyden chamber technique) using the CD9 positive TEL/AML1-positive cell line REH and the CD9 negative cell line RAJI (wild or transfected with CD9 cDNA). Data will be analyzed in combination with blocking antibodies and chemical antagonist according to the level of CD9 (transcript and protein) and of CXCR4. Protein quantifications will be performed by flow cytometry and Western Blot. Interactions will be explored by confocal microscopy and biological pathways by immunoblot.

    Adhesion results will be validated on patient samples of B-ALL.

    Other Name: Not Apllicable
    Other: Post-transcriptional regulation of CD9

    2) Post-transcriptional regulation of CD9 in TEL/AML1-positive ALL To identify miRNAs that are potentially deregulated in TEL/AML1-positive acute lymphoblastic leukaemia and especially to screen for CD9 -targeted miRNAs, we will use a TaqMan ®MicroRNA Arrays approach allowing the simultaneous measurement of about 760 human miRNA.

    Small RNA will be extracted from bone marrow samples of twenty childhood B-ALL to screen miRNAs which are differentially expressed between CD9-positive and CD9-negative ALL and further compared with miRNAs which were predicted to target CD9 in databases. Validation of the selection will be performed by single Q-PCR for selected miRNAs using a novel cohort of ten bone marrow samples.

    Other Name: Not Apllicable
Detailed Description:
  1. Assess of the impact of CD9 expression level on motility assays (migration and adhesion) We have initiated motility assays (fibronectin adhesion experiments and CXCL12 chemoattracted migration tests with modified Boyden chamber technique) using the CD9 positive TEL/AML1-positive cell line REH and the CD9 negative cell line RAJI (wild or transfected with CD9 cDNA). Data will be analyzed in combination with blocking antibodies and chemical antagonist according to the level of CD9 (transcript and protein) and of CXCR4. Protein quantifications will be performed by flow cytometry and Western Blot. Interactions will be explored by confocal microscopy and biological pathways by immunoblot.

    Adhesion results will be validated on patient samples of B-ALL.

  2. Post-transcriptional regulation of CD9 in TEL/AML1-positive ALL To identify miRNAs that are potentially deregulated in TEL/AML1-positive acute lymphoblastic leukaemia and especially to screen for CD9 -targeted miRNAs, we will use a TaqMan ®MicroRNA Arrays approach allowing the simultaneous measurement of about 760 human miRNA.

Small RNA will be extracted from bone marrow samples of twenty childhood B-ALL to screen miRNAs which are differentially expressed between CD9-positive and CD9-negative ALL and further compared with miRNAs which were predicted to target CD9 in databases. Validation of the selection will be performed by single Q-PCR for selected miRNAs using a novel cohort of ten bone marrow samples. Transfection assays and luciferase assays will be further realized to confirm that the differential miRNAs really target and affect CD9 expression .

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients > 1 year and ≤18 years
  • with B-ALL diagnosis
  • registered in Rennes for treatment
  • written informed consent signed by all patients or their parents or legal guardian

Exclusion Criteria:

  • Refusal to participate
  • Inherited cytogenetic abnormalities
  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 ClinicalTrials.gov identifier: NCT01282593

Contacts
Contact: Virginie Gandemer, MD 02.99.26.67.48 virginie.gandemer@chu-rennes.fr

Locations
France
Rennes University Hospital Recruiting
Rennes, France, 35000
Contact: Virginie Gandemer, MD    02.99.226.67.48    vriginie.gandemer@chu-rennes.fr   
Contact: Isabelle Debroise, Study Nurse    02.99.26.30.41    isabelle.debroise@chu-rennes.fr   
Principal Investigator: Virginie Gandemer, MD         
Sponsors and Collaborators
Rennes University Hospital
Ligue contre le cancer, France
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01282593     History of Changes
Other Study ID Numbers: LOC/10-05, 2010-A00622-37, B100651-40
Study First Received: January 24, 2011
Last Updated: January 3, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Rennes University Hospital:
TEL/ALM1_positive ALL relapses

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 27, 2014