NCT01282593

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
51

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Nov 2010

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2010

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

January 24, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 25, 2011

Completed
7.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 11, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 11, 2018

Completed
Last Updated

May 24, 2023

Status Verified

May 1, 2023

Enrollment Period

7.9 years

First QC Date

January 24, 2011

Last Update Submit

May 22, 2023

Conditions

Acute Lymphoblastic Leukemia (ALL)

Keywords

TEL/ALM1_positive ALL relapses

Outcome Measures

Primary Outcomes (1)

  • 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

    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

    3 years

Secondary Outcomes (3)

  • - Migratory potential of blasts according to CD9 expression

    3 years

  • - Adhesion properties of blasts according to CD9 expression

    3 years

  • - Level of miRNA, that could affect CD9 transcript levels inTEL/AML1-positive blasts versus TEL/AML1-negative ones

    3 years

Study Arms (1)

CD9 expression level

OTHER

Impact of CD9 expression level on motility assays

Other: Impact of CD9 expression level on motility assaysOther: Post-transcriptional regulation of CD9

Interventions

Impact of CD9 expression level on motility assaysOTHER

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.

Also known as: Not Apllicable
CD9 expression level
Post-transcriptional regulation of CD9OTHER

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.

Also known as: Not Apllicable
CD9 expression level

Eligibility Criteria

Age1 Year - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • Refusal to participate
  • Inherited cytogenetic abnormalities

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Rennes University Hospital

Rennes, 35000, France

Location

Related Publications (6)

  • Debaize L, Jakobczyk H, Avner S, Gaudichon J, Rio AG, Serandour AA, Dorsheimer L, Chalmel F, Carroll JS, Zornig M, Rieger MA, Delalande O, Salbert G, Galibert MD, Gandemer V, Troadec MB. Interplay between transcription regulators RUNX1 and FUBP1 activates an enhancer of the oncogene c-KIT and amplifies cell proliferation. Nucleic Acids Res. 2018 Nov 30;46(21):11214-11228. doi: 10.1093/nar/gky756.

    PMID: 30500954RESULT

  • Arnaud MP, Vallee A, Robert G, Bonneau J, Leroy C, Varin-Blank N, Rio AG, Troadec MB, Galibert MD, Gandemer V. CD9, a key actor in the dissemination of lymphoblastic leukemia, modulating CXCR4-mediated migration via RAC1 signaling. Blood. 2015 Oct 8;126(15):1802-12. doi: 10.1182/blood-2015-02-628560. Epub 2015 Aug 28.

    PMID: 26320102RESULT

  • Gaudichon J, Jakobczyk H, Debaize L, Cousin E, Galibert MD, Troadec MB, Gandemer V. Mechanisms of extramedullary relapse in acute lymphoblastic leukemia: Reconciling biological concepts and clinical issues. Blood Rev. 2019 Jul;36:40-56. doi: 10.1016/j.blre.2019.04.003. Epub 2019 Apr 17.

    PMID: 31010660RESULT

  • Rouger-Gaudichon J, Cousin E, Jakobczyk H, Debaize L, Rio AG, Forestier A, Arnaud MP, Villacreces A, Praloran V, Jacamo R, Galibert MD, Troadec MB, Gandemer V. Hypoxia regulates CD9 expression and dissemination of B lymphoblasts. Leuk Res. 2022 Dec;123:106964. doi: 10.1016/j.leukres.2022.106964. Epub 2022 Sep 28.

    PMID: 36335655RESULT

  • Debaize L, Jakobczyk H, Rio AG, Gandemer V, Troadec MB. Optimization of proximity ligation assay (PLA) for detection of protein interactions and fusion proteins in non-adherent cells: application to pre-B lymphocytes. Mol Cytogenet. 2017 Jul 20;10:27. doi: 10.1186/s13039-017-0328-2. eCollection 2017.

    PMID: 28736577RESULT

  • Jakobczyk H, Debaize L, Soubise B, Avner S, Rouger-Gaudichon J, Commet S, Jiang Y, Serandour AA, Rio AG, Carroll JS, Wichmann C, Lie-A-Ling M, Lacaud G, Corcos L, Salbert G, Galibert MD, Gandemer V, Troadec MB. Reduction of RUNX1 transcription factor activity by a CBFA2T3-mimicking peptide: application to B cell precursor acute lymphoblastic leukemia. J Hematol Oncol. 2021 Mar 20;14(1):47. doi: 10.1186/s13045-021-01051-z.

    PMID: 33743795RESULT

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 24, 2011

First Posted

January 25, 2011

Study Start

November 1, 2010

Primary Completion

October 11, 2018

Study Completion

October 11, 2018

Last Updated

May 24, 2023

Record last verified: 2023-05

Locations

FR(1)