CD36 cell surface expression as a surrogate marker to identify ABL/JAK-class kinase fusions in pediatric BCP-ALL

Marion Strullu ^1,2,3, Aurélie Caye-Eude ⁴, Elie Robert ⁵

¹Pediatric Hematology and Immunology Department, Robert-Debré Hospital (Assistance Publique-Hôpitaux de Paris (APHP)), Paris, France.
²University of Paris Cité, Paris, France.
³INSERM U1131, IUH, Paris, France.
⁴Genetic Department, Robert-Debré Hospital, APHP, Paris, France.
⁵INSERM U1170, Gustave Roussy Cancer Campus, Université Paris Saclay, PEDIAC Program, Villejuif, France.
⁶Hematology Laboratory, Robert-Debré Hospital, APHP, Paris, France.
⁷Genetic Department, Armand Trousseau, APHP, Paris, France.
⁸Hematology Laboratory, Saint-Louis Hospital, APHP, Paris, France.
⁹Department of Pediatric Oncology and Hematology, CHU Montpellier, Montpellier, France.
¹⁰Department of Pediatric Onco-hematology, CHU de Saint-Etienne, Saint-Etienne, France.
¹¹Department of Pediatric Hematology-Oncology, CHU de Strasbourg, Strasbourg, France.
¹²Department of Pediatric Onco-hematology, Sorbonne University, Armand Trousseau Hospital, APHP, Paris, France.
¹³Pediatric Hematology-Oncology Department, CHU de Nice, Université de Côte d'Azur, Nice, France.
¹⁴URP-3518, Institut de Recherche Saint-Louis, Paris, France.
¹⁵University of Paris Cité, Paris, France. elodie.lainey@aphp.fr.
¹⁶INSERM U1131, IUH, Paris, France. elodie.lainey@aphp.fr.
¹⁷Hematology Laboratory, Robert-Debré Hospital, APHP, Paris, France. elodie.lainey@aphp.fr.

⁰Pediatric Hematology and Immunology Department, Robert-Debré Hospital (Assistance Publique-Hôpitaux de Paris (APHP)), Paris, France.

Leukemia +

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October 17, 2024

View abstract on PubMed

Summary

Identifying specific immunophenotypic features can rapidly screen for Philadelphia-like kinase fusions in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This flow cytometry method aids in timely treatment decisions for high-risk BCP-ALL patients.

Area Of Science

Hematology
Molecular Biology
Immunophenotyping

Background

Genetic alterations are crucial for risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
ABL-class fusions in BCP-ALL are high-risk but respond well to tyrosine kinase inhibitors (TKIs).
Rapid identification of these genetic alterations is essential for timely TKI treatment initiation.

Purpose Of The Study

To investigate if immunophenotypic features can serve as a screening tool for ABL-class and JAK-class kinase fusions in BCP-ALL.
To develop a predictive scoring system for genetic subtypes with aberrant kinase activation.
To differentiate ABL-class from JAK-class kinase fusions using immunophenotypes.

Main Methods

Utilized flow cytometry to analyze immunophenotypic characteristics of BCP-ALL samples.
Assessed expression of markers like CD36, TSLPR, CD19, CD22, CD9, CD38, CD81, CD304, and CD49f.
Developed a multiparameter scoring system to predict genetic subtypes.

Main Results

CD36 expression was identified as a characteristic feature of ABL- or JAK-class kinase fusions.
Specific immunophenotypic profiles were associated with distinct genetic subgroups within Philadelphia-like BCP-ALL.
The developed scoring system effectively segregated genetic subtypes with aberrant kinase activation.
TSLPR in combination with CD19/22/9/38/81/304 and CD49f emerged as robust predictive markers.
Immunophenotypes distinguishing ABL from JAK-class fusions were identified.

Conclusions

Flow cytometry offers a sensitive (95%) and specific (96%) method for rapid screening of Philadelphia-like kinase fusions in BCP-ALL.
This approach can significantly aid in identifying patients who would benefit from TKI therapy.
The method is accessible to most hematology departments, facilitating wider clinical application.