Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion

Wrona,Ewa; Jakubowska,Justyna; Pawlik,Bartłomiej; Pastorczak,Agata; Madzio,Joanna; Lejman,Monika; Sędek,Łukasz; Kowalczyk,Jerzy; Szczepański,Tomasz; Młynarski,Wojciech

doi:10.3892/ol.2019.11046

Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion

Authors:
- Ewa Wrona
- Justyna Jakubowska
- Bartłomiej Pawlik
- Agata Pastorczak
- Joanna Madzio
- Monika Lejman
- Łukasz Sędek
- Jerzy Kowalczyk
- Tomasz Szczepański
- Wojciech Młynarski
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Affiliations: Department of Chemotherapy, Medical University of Lodz, Lodz 91‑738, Poland, Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz 91‑738, Poland, Department of Pediatric Hematology and Oncology, Medical University of Lublin, Lublin 20‑093, Poland, Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Zabrze, Katowice 40‑752, Poland, Department of Pediatric Hematology and Oncology, Medical University of Silesia in Katowice, Zabrze, Katowice 40‑752, Poland
Published online on: November 4, 2019 https://doi.org/10.3892/ol.2019.11046
Pages: 6926-6932

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Abstract

Resistance to L‑asparaginase (L‑asp) is a major contributor to poor treatment outcomes of several subtypes of childhood B cell precursor acute lymphoblastic leukemia (BCP‑ALL). Asparagine synthetase (ASNS), legumain (LGMN) and cathepsin B (CTSB) serve a key role in L‑asp resistance. The association between genetic subtypes of BCP‑ALL and the expression of ASNS, LGMN and CTSB may elucidate the mechanisms of treatment failure. Bone marrow samples of 52 children newly diagnosed with BCP‑ALL were screened for major genetic abnormalities and ASNS, LGMN and CTSB gene expression levels. The cohort was further divided into groups corresponding to the key genetic aberrations occurring in BCP‑ALL: Breakpoint cluster region and Abelson murine leukemia viral oncogene homolog 1 fusion; hyperdiploidy, hypodiploidy, ETS variant 6 and runt‑related transcription factor 1 fusion and other BCP‑ALL with no primary genetic aberration identified. A subgroup analysis based on the differences in copy number variations demonstrated a significant increase of ASNS, LGMN and CTSB median expression in other BCP‑ALL cases with paired box 5 (PAX5) deletion (P=0.0117; P=0.0036; P<0.0001, respectively) compared with those with wild‑type PAX5. Patients with high ASNS expression exhibited longer relapse‑free survival (RFS) compared with those with low ASNS levels (P=0.0315; HR, 0.19; 95% CI, 0.04‑0.86); the 5‑year RFS for patients in the high ASNS expression group was 90.15% (95% CI, 87.90‑92.40%). Despite the impact on ASNS, LGMN and CTSB expression, PAX5 deletion did not influence RFS in the other BCP‑ALL group (P=0.6839). Therefore, the results of the present study revealed high levels of ASNS, LGMN and CTSB expression in the other BCP‑ALL group with concomitant PAX5 deletion and no subsequent deterioration in 5‑year RFS. High ASNS expression level, as a single factor, was strongly associated with an improved outcome.

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