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PAX5 Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol.
Crepinsek, Klementina; Klobucar, Nika; Tesovnik, Tine; Sket, Robert; Jenko Bizjan, Barbara; Kovac, Jernej; Kavcic, Marko; Prelog, Tomaz; Kitanovski, Lidija; Jazbec, Janez; Debeljak, Marusa.
Affiliation
  • Crepinsek K; Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia.
  • Klobucar N; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
  • Tesovnik T; Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia.
  • Sket R; Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia.
  • Jenko Bizjan B; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
  • Kovac J; Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia.
  • Kavcic M; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
  • Prelog T; Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia.
  • Kitanovski L; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
  • Jazbec J; Clinical Institute for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia.
  • Debeljak M; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Cancers (Basel) ; 16(6)2024 Mar 15.
Article in En | MEDLINE | ID: mdl-38539499
ABSTRACT
In this study, we aimed to identify patients within our B-ALL cohort with altered PAX5. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children's Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study. We used RNA sequencing data for gene expression analysis, fusion gene detection and single nucleotide variant identification, multiplex-ligation dependent probe amplification for copy number variation assessment, and Sanger sequencing for germline variant detection. PAX5 was impacted in 33.3% of our patients, with the genetic alterations ranging from CNVs and rearrangements to SNVs. The most common were CNVs, which were found in more than a third of patients, followed by point mutations in 5.2%, and gene rearrangements in 4.1%. We identified eight patients with a PAX5-associated genetic subtype that were previously classified as "B-other", and they showed intermediate outcomes. We showed higher minimal residual disease values at the end of induction and poorer event-free survival in hyperdiploid cases carrying duplications in PAX5 compared to other hyperdiploid cases. We also report an interesting case of a patient with PAX5FKBP15 and a pathogenic variant in PTPN11 who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diverse PAX5 alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2024 Document type: Article Affiliation country: Slovenia

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2024 Document type: Article Affiliation country: Slovenia