• Medical diagnostics
  • MPN
  • ALL
  • CLL
  • AML
  • Targeted therapy
  • Chemotherapy
  • Clinical research (TRL 6-8)
  • Real-world research (TRL 9)

Development of medical diagnostic kits using NGS technology, for the detection of mutations in acute leukemia, at the hematology laboratory of Toulouse University Hospital.

The clinical management of leukemia is based on the results of cytology, flow cytometry, cytogenetics and molecular biology in a time frame increasingly constrained by the arrival of new targeted therapies used in induction of treatments. To respond to this challenge, we have developed rapid (3 days) and sensitive (0.5%) diagnostic methods based on restricted panels adapted to specific clinical requests tested for 7 years in the hematology laboratory of the Toulouse University Hospital. These techniques are Cofrac and EFI accredited (chimerism).

Description

Scope of the offer

Molecular medical diagnosis of leukemias.

Our original offer (design, production, validation of methods, Cofrac accreditation) of molecular diagnostics combined to extensive analyzes of leukemia makes it possible to respond to 2 clinical requests:

  • A quick response in 3 days
  • A very specific analysis of leukemia mutations, answering very precise clinical questions, critical for either patients monitoring, their diagnosis, or the use of a targeted treatment without the necessary need for an extensive analysis, allowing cost savings (reagent cost of around €15 per sample)

The analyzes carried out by a similar procedure allowing their combination concern:

  • Acute myeloid leukemia (392 carried out in 2022)
  • Myelodysplastic syndromes and myelodysplastic syndromes/myeloproliferative syndromes (622 carried out in 2022)
  • Myeloproliferative neoplasia (essential thrombocythemia, polycythemia vera, myelofibrosis, mastocytosis, atypical CML; 2,083 carried out in 2022)
  • Lymphoproliferative syndromes (641 carried out in 2022)
  • Resistance to innovative therapies (364 carried out in 2022)
  • Post-allograft chimerism (1149 performed in 2022)

Conduct of studies

Steps :

  • Analysis of the diagnostic need
  • Design
  • Realization
  • Method validation
  • Cofrac accreditation

Research infrastructure

The molecular biology department of the hematology laboratory of the Toulouse University Hospital analyzes 5,000 patients suspected of hematologic malignancies and 10,000 samples per year. More than half of the molecular analyzes are carried out by next generation sequencing (NGS), either by restricted panel (proposed offer) or by expanded panel (bringing together 80 to 100 genes depending on the panels).

Experimental and analysis platforms:

  • Genomics: analyzes are carried out on Illumina sequencers (MiSeq, NextSeq500, NovaSeq6000). The platform has 3 Hamilton robots and a Magnis robot in a circuit secured by the use of 2D tubes allowing the traceability of analytical monitoring

Technical personnel:

  • 5 technicians
  • 2 engineers
  • 3 medical biologists

Quality assurance

The molecular biology department of the hematology laboratory of Toulouse University Hospital is Cofrac, EFI, ERICLL accredited and relies on external quality assessments from GBMHM and UKNeqas.

Specifications

  • The platform

Development of NGS analyses for medical diagnosis of hematological malignancies.

  • The studies

NGS analysis :

  • Acute myeloid leukemias (AML restricted panel: ASXL1 (exon 12), DDX41 (exon 15), DNMT3A (exon 23), FLT3 (exons 16 and 20), IDH1 (exon 4), IDH2 (exon 4), NPM1 (exon 12))
  • Myelodysplastic syndromes and myelodysplastic/myeloproliferative syndromes (restricted panel AML + restricted panel MDS: SF3B1 (exons 14 and 15), SRSF2 (exon 1, U2AF1 (exons 2 and 6), UBA1 (exon 3) +/- restricted panel RAS: KRAS (exons 2 and 3), NRAS (exons 2 and 3))
  • Myeloproliferative neoplasia (essential thrombocythemia, Vaquez polyglobulia, myelofibrosis: SMP restricted panel: CALR (exon 9, JAK2 (exons 12 and 14), MPL (exon 10); mastocytosis : Mastocytosis restricted panel: KIT (exons 8, 9, 11, 13 and 17); Atypical CML: Atypical CML restricted panel: CSF3R (exons 14, 15, 16 and 17), ETNK1 (exon 3), SETBP1 (exon 4))
  • Lymphoproliferative disorders (restricted panel SLP-B: BRAF (exon 15), CXCR4 (exon 2), MYD88 (exon 5), SPI1 (exon 5); restricted panel SLP-T: STAT3 (exons 20 and 21), STAT5B (exon 16))
  • Resistance to innovative therapies (Resistance restricted panel: BCL2 (exon 2), BTK (exons 15 and 16), PLCG2 (exons 19, 20, 24, 27 and 30); TP53 restricted panel: TP53 (exons 2, 3, 4, 5, 6, 7, 8, 9,10 and 11))
  • Post-allograft chimerism (44 markers assessed at diagnosis, 2 per chromosome; 6 markers distinguishing recipient and donor during follow-up)

Examples of partnerships

COVENIDAC, randomization R4, NCT02416388 - Rapid molecular typing of patients included in the BIG1 protocol, randomization R4-COVENIDAC using the AML restricted panel (454 patients tested)

Partner: FILO-AML

 

PHRC INTER REGIONAL EVATRYMS, NCT02441166- Rapid molecular typing of patients included in the Evatryms PHRC using the KIT restricted panel for validation of mastocytosis status (219 patients tested)

Partner: Dermatology Department, Toulouse University Hospital.

Terms

OPALE entity

CRCT (UMR-1037)

CRCT (UMR-1037)
Eric Delabesse
Prof. Eric Delabesse
Head of Entity (IGAALD)

Contact

Sandrine Palcy Dr. Sandrine Palcy
Business Development Director

Other offers

Contact us