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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-A00622-37 | Registry Identifier | ID RCB | |
| B100651-40 | Registry Identifier | AFSSAPS reference |
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| Name | Class |
|---|---|
| Ligue contre le cancer, France | OTHER |
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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).
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.
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 .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CD9 expression level | Other | Impact of CD9 expression level on motility assays |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Impact of CD9 expression level on motility assays | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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.
| 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| - Migratory potential of blasts according to CD9 expression | - Migratory potential of blasts according to CD9 expression | 3 years |
| - Adhesion properties of blasts according to CD9 expression | - Adhesion properties of blasts according to CD9 expression |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rennes University Hospital | Rennes | 35000 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30500954 | Result | 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. | |
| 26320102 |
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|
| Post-transcriptional regulation of CD9 | Other | 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. |
|
|
| 3 years |
| - Level of miRNA, that could affect CD9 transcript levels inTEL/AML1-positive blasts versus TEL/AML1-negative ones | - Level of miRNA, that could affect CD9 transcript levels inTEL/AML1-positive blasts versus TEL/AML1-negative ones | 3 years |
| Result |
| 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. |
| 31010660 | Result | 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. |
| 36335655 | Result | 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. |
| 28736577 | Result | 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. |
| 33743795 | Result | 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. |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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