PAX5::AUTS2 childhood B-ALL: a relapse-prone genetic subtype with frequent central nervous system involvement and a poor outcome

Aurélie Caye-Eude^{1

2}, Grazia Fazio^{3

4}, Agata Pastorczak⁵, Judith M Boer⁶, Doris Steinemann⁷, Debdutta Ganguli⁸, Edwin Sonneveld^{6

9}, Sabrina Haslinger^{10

11}, Lucía D'Andrea¹², Jutta Bradtke¹³, Bruno A Lopes¹⁴, Marketa Zaliova^{15

16

17}, Gabriele Escherich¹⁸, Margit König^{10

11}, Klaus Fortschegger¹⁰, Andrea Inthal^{10

11}, Irina Stasevich¹⁹, Mariana Emerenciano²⁰, Jan Trka^{15

16

17}, Luis Castillo¹², Mayur Parihar²¹, Anthony V Moorman²², Anke K Bergmann⁷, Monique L den Boer⁶, Wojciech Młynarski²³, Giovanni Cazzaniga^{3

4}, Hélène Cavé^{1

2}, Karin Nebral^{10

11}, Dagmar Schinnerl¹⁰, Sabine Strehl²⁴

Affiliations

¹ Department of Genetics, University Hospital Robert Debré, Paris, France.
² INSERM UMR_S1131, Institut de Recherche Saint-Louis, Université Paris-Cité, Paris, France.
³ Tettamanti Center, Fondazione IRCCS, San Gerardo dei Tintori, Monza, Italy.
⁴ School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
⁵ Department of Genetic Predisposition to Cancer, Medical University of Łódź, Łódź, Poland.
⁶ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
⁷ Department of Human Genetics, Hannover Medical School, Hannover, Germany.
⁸ Administrative-Lead Genomics, Tata Translational Cancer Research Center/Tata Medical Center, Kolkata, India.
⁹ Dutch Childhood Oncology Group (DCOG), Utrecht, The Netherlands.
¹⁰ St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
¹¹ Labdia Labordiagnostik, Vienna, Austria.
¹² Department of Pediatric Hematology and Oncology, Hospital Pereira Rossell, Pérez Scremini Foundation, Montevideo, Uruguay.
¹³ Universitätsklinikum Gießen und Marburg, Institut für Pathologie, Onkogenetisches Labor Molekularpathologie, Gießen, Germany.
¹⁴ Leukemia DataLab, Instituto Nacional de Câncer-INCA, Rio de Janeiro, Brazil.
¹⁵ CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
¹⁶ Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁷ University Hospital Motol, Prague, Czech Republic.
¹⁸ University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁹ NHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
²⁰ Genetics of Acute Leukaemia Laboratory-GenLAb, Instituto Nacional de Câncer-INCA, Rio de Janeiro, Brazil.
²¹ Department of Laboratory Haematology and Cytogenetics, Tata Medical Centre, Kolkata, India.
²² Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
²³ Department of Pediatrics, Oncology and Hematology, Medical University of Łódź, Łódź, Poland.
²⁴ St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria. sabine.strehl@ccri.at.

PMID: 39702796
PMCID: PMC11794147
DOI: 10.1038/s41375-024-02502-5

PAX5::AUTS2 childhood B-ALL: a relapse-prone genetic subtype with frequent central nervous system involvement and a poor outcome

Aurélie Caye-Eude et al. Leukemia. 2025 Feb.

. 2025 Feb;39(2):482-486.

doi: 10.1038/s41375-024-02502-5. Epub 2024 Dec 19.

Authors

Affiliations

¹ Department of Genetics, University Hospital Robert Debré, Paris, France.
² INSERM UMR_S1131, Institut de Recherche Saint-Louis, Université Paris-Cité, Paris, France.
³ Tettamanti Center, Fondazione IRCCS, San Gerardo dei Tintori, Monza, Italy.
⁴ School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
⁵ Department of Genetic Predisposition to Cancer, Medical University of Łódź, Łódź, Poland.
⁶ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
⁷ Department of Human Genetics, Hannover Medical School, Hannover, Germany.
⁸ Administrative-Lead Genomics, Tata Translational Cancer Research Center/Tata Medical Center, Kolkata, India.
⁹ Dutch Childhood Oncology Group (DCOG), Utrecht, The Netherlands.
¹⁰ St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria.
¹¹ Labdia Labordiagnostik, Vienna, Austria.
¹² Department of Pediatric Hematology and Oncology, Hospital Pereira Rossell, Pérez Scremini Foundation, Montevideo, Uruguay.
¹³ Universitätsklinikum Gießen und Marburg, Institut für Pathologie, Onkogenetisches Labor Molekularpathologie, Gießen, Germany.
¹⁴ Leukemia DataLab, Instituto Nacional de Câncer-INCA, Rio de Janeiro, Brazil.
¹⁵ CLIP (Childhood Leukaemia Investigation Prague), Prague, Czech Republic.
¹⁶ Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁷ University Hospital Motol, Prague, Czech Republic.
¹⁸ University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁹ NHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
²⁰ Genetics of Acute Leukaemia Laboratory-GenLAb, Instituto Nacional de Câncer-INCA, Rio de Janeiro, Brazil.
²¹ Department of Laboratory Haematology and Cytogenetics, Tata Medical Centre, Kolkata, India.
²² Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
²³ Department of Pediatrics, Oncology and Hematology, Medical University of Łódź, Łódź, Poland.
²⁴ St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria. sabine.strehl@ccri.at.

PMID: 39702796
PMCID: PMC11794147
DOI: 10.1038/s41375-024-02502-5

Abstract

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was conducted in accordance with the ethical standards of the institutional and/or national research committees and with the ethical standards as laid down in the Declaration of Helsinki, and all methods were performed in accordance with the relevant guidelines and regulations. Patients were enrolled in an approved international or national clinical trial with written informed consent from their parents or legal guardians. The institutional review boards of the participating study groups approved the use of anonymized patient data for research purposes.

Figures

**Fig. 1. Course of disease and outcome of *PAX5*::*AUTS2* patients.**
A Swimmer plot illustrating the clinical course of each individual patient. Relapses (orange dots), bone marrow transplantation (BMT; blue triangles), and death (red crosses) as well as age groups <18 months (light brown bars) and ≥18 months (gray bars) are indicated. B–C Cumulative incidence of relapse (CIR) and Kaplan-Meier survival curves of event-free (EFS) and overall survival (OS), (B) of all *PAX5*::*AUTS2* cases (n = 50), (C) based on age group; red, <18 months; blue, ≥18 months. Gray’s test p-value for CIR, Log-ranks test p-values for EFS and OS. D Forrest plot showing results of multivariate Cox regression analysis. HR hazard ratio, CI confidence interval, p Gray’s test p-value, WBC white blood cell count, NCI-HR National Cancer Institute high-risk, MRD-EOI (measurable residual disease) determined by PCR and/or flow cytometry at the end of induction (EOI) therapy.

See this image and copyright information in PMC

References

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PAX5::AUTS2 childhood B-ALL: a relapse-prone genetic subtype with frequent central nervous system involvement and a poor outcome

Affiliations

PAX5::AUTS2 childhood B-ALL: a relapse-prone genetic subtype with frequent central nervous system involvement and a poor outcome

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources