Implementation of Innovative Techniques in Routine Diagnosis of Childhood Acute Leukemia: Analysis of Genome and Transcriptome by Micro-array

Acute leukemias are a heterogeneous group of malignancies characterized by the abnormal proliferation of a cell clone in the bone marrow, having as origin lymphocytic or myeloid lineage. The repertoire of mutations that determine the leukemic transformation, complex and variable depending on the tumor type and progression of the disease, combined in the same cell of balanced and unbalanced chromosomal aberrations, point mutations and epigenetic abnormalities.

The project presented here is part of a comprehensive approach to diagnosis of hematologic malignancies of children. Using comparative genomic hybridization on microarray (or array- CGH) and transcriptome analysis by microarray, two innovative techniques for a comprehensive analysis of the genome and transcriptome , offer new perspectives identifying molecular defects . These techniques provide new elements in the identification of acute leukemia at diagnosis may identify new prognostic factors to optimize the care of patients.

This project involves both the Department of Medical Genetics (Prof. N. LEVY ) regarding the identification of genomic abnormalities associated with childhood leukemia , the Laboratory of Hematology of the Hospital de la Timone ( Prof. Pierre Morange ) in terms of the phenotypic characterization of tumor cells, and the Onco - Hematology Pediatric Department (Prof. Michel Gerard ) which provides diagnosis, treatment , monitoring and the bone marrow of children with hematologic malignancies . The following project is mainly focused on the identification of genomic abnormalities (deletions and duplications) and abnormalities in gene expression to identify a genetic profile ensuring a better classification within the different groups risk .

The project we propose is centered on the identification of genomic abnormalities , changing the number of copies of certain regions of the genome or determining loss of heterozygosity , and the identification of changes in the level of gene expression by using two analytical techniques, comparative genomic hybridization on microarray (or array- CGH) and expression studies with microarrays . The data generated will , for the identification of " molecular signatures " , the classification of patients according to prognosis , variations in treatment response and survival.

The originality of this project lies in the use of these new tools in the diagnosis of hematological malignancies in children. This pilot study will be conducted with commercial Affymetrix , will develop the chips ' processing' , dedicated , enriched probes corresponding to genes involved in leukemogenesis , with high discriminatory power in identifying these signatures.

The data published in the specialized literature from the study of large series of patients show that microarrays provide important information for the diagnosis and therapeutic management of patients. It is for this reason that in the end we hope to integrate these analyzes in routine diagnosis to complement other analyzes ( phenotyping , identification of fusion genes and sequencing) in order to further characterize the abnormal cells leukemia and establish an " identity card of leukemia .

Study Overview

• Status: Completed
• Conditions: Acute Leukemia
• Intervention / Treatment: Genetic: blood draw

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cornel POPOVICI; Email: cornel.popovici@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients aged 0-18 years with a diagnosis of acute leukemia

Exclusion Criteria:

• patients without leukemia diagnosis
• patients for which the quantities obtained from DNA and RNA are insufficient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: blood sample	Genetic: blood draw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
identification of genomic abnormalities	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
changing the number of copies of certain regions of the genome or determining loss of heterozygosity	24 months
identification of changes in the level of gene expression	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: Urielle DESALBRES, Assistance Publique Hôpitaux de Marseille, 80 rue Brochier, 13354 Marseille Cedex 05

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2014
• Primary Completion (Actual): May 26, 2016
• Study Completion (Actual): July 27, 2023

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: January 14, 2014
• First Posted (Estimated): January 16, 2014

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Acute Disease
• Other Study ID Numbers: 2013-A00263-42; 2013-05 (Other Identifier: Assistance Publique Hôpitaux de Marseille)