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Article

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
  • View Affiliations / Copyright

    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
  • Pages: 6926-6932
    |
    Published online on: November 4, 2019
       https://doi.org/10.3892/ol.2019.11046
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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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1 

Pieters R, Appel I, Kuehnel HJ, Tetzlaff-Fohr I, Pichlmeier U, Van Der Vaart I, Visser E and Stigter R: Pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant asparaginase preparation in children with previously untreated acute lymphoblastic leukemia: A randomized phase 2 clinical trial. Blood. 112:4832–4838. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Appel IM, Den Boer ML, Meijerink JP, Veerman AJ, Reniers NC and Pieters R: Up-regulation of asparagine synthetase expression is not linked to the clinical response to L-asparaginase in pediatric acute lymphoblastic leukemia. Blood. 107:4244–4249. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, Van Zutven LJ, Beverloo HB, Van der Spek PJ, Escherich G, et al: A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: A genome-wide classification study. Lancet Oncol. 10:125–134. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Richards NG and Kilberg MS: Asparagine synthetase chemotherapy. Annu Rev Biochem. 75:629–654. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Su N, Pan YX, Zhou M, Harvey RC, Hunger SP and Kilberg MS: Correlation between asparaginase sensitivity and asparagine synthetase protein content, but not mRNA, in acute lymphoblastic leukemia cell lines. Pediatr Blood Cancer. 50:274–279. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Accordi B, Galla L, Milani G, Curtarello M, Serafin V, Lissandron V, Viola G, te Kronnie G, De Maria R, Petricoin EF III, et al: AMPK inhibition enhances apoptosis in MLL-rearranged pediatric B-acute lymphoblastic leukemia cells. Leukemia. 27:1019–1027. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Dimitriou H, Choulaki C, Perdikogianni C, Stiakaki E and Kalmanti M: Expression levels of ASNS in mesenchymal stromal cells in childhood acute lymphoblastic leukemia. Int J Hematol. 99:305–310. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Chien WW, Le Beux C, Rachinel N, Julien M, Lacroix CE, Allas S, Sahakian P, Cornut-Thibaut A, Lionnard L, Kucharczak J, et al: Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines. Sci Rep. 5:80682015. View Article : Google Scholar : PubMed/NCBI

9 

Patel N, Krishnan S, Offman MN, Krol M, Moss CX, Leighton C, van Delft FW, Holland M, Liu J, Alexander S, et al: A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase. J Clin Invest. 119:1964–1973. 2009.PubMed/NCBI

10 

Hermanova I, Zaliova M, Trka J and Starkova J: Low expression of asparagine synthetase in lymphoid blasts precludes its role in sensitivity to L-asparaginase. Exp Hematol. 40:657–665. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Krejci O, Starkova J, Otava B, Madzo J, Kalinova M, Hrusak O and Trka J: Upregulation of asparagine synthetase fails to avert cell cycle arrest induced by L-asparaginase in TEL/AML1-positive leukemic cells. Leukemia. 18:434–441. 2004. View Article : Google Scholar : PubMed/NCBI

12 

He Y, Li B, Luo C, Shen S, Chen J, Xue H, Tang J and Gu L: Asparagine synthetase is partially localized to the plasma membrane and upregulated by L-asparaginase in U937 cells. J Huazhong Univ Sci Technol Med Sci. 31:159–163. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Lomelino CL, Andring JT, McKenna R and Kilberg MS: Asparagine synthetase: Function, structure, and role in disease. J Biol Chem. 292:19952–19958. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Strefford JC, van Delft FW, Robinson HM, Worley H, Yiannikouris O, Selzer R Richmond T, Hann I, Bellotti T, Raghavan M, et al: Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Proc Natl Acad Sci USA. 103:8167–8172. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Stams WA, Den Boer ML, Beverloo HB, Meijerink JP, Stigter RL, Van Wering ER, Janka-Schaub GE, Slater R and Pieters R: Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+pediatric ALL. Blood. 101:2743–2747. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Aslanian AM, Fletcher BS and Kilberg MS: L-asparaginase resistance in MOLT-4 human leukaemia cells. Biochem J. 357:321–328. 2001. View Article : Google Scholar : PubMed/NCBI

17 

International BFM Study Group, : A randomized trial of the I-BFM-SG for the management of childhood ALL IC-BFM. 2009.

18 

Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, Gonzalez A, Izraeli S, Janic D, Jazbec J, et al: Intensive chemotherapy for childhood acute lymphoblastic leukemia: Results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 32:174–184. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Wingender E: TheTRANSFAC project as an example of framework technology that supports the analysis of genomic regulation. Brief Bioinform. 9:326–332. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Wenzinger C, Williams E and Gru AA: Updates in the pathology of precursor lymphoid neoplasms in the revised fourth edition of the WHO classification of tumors of hematopoietic and lymphoid tissues. Curr Hematol Malig Rep. 13:275–288. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Moorman AV: New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia. Haematologica. 101:407–416. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Schwab C, Nebral K, Chilton L, Leschi C, Waanders E, Boer JM, Žaliová M, Sutton R, Öfverholm II, Ohki K, et al: Intragenic amplification of PAX5: A novel subgroup in B-cell precursor acute lymphoblastic leukemia? Blood Adv. 1:1473–1477. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wrona E, Jakubowska J, Pawlik B, Pastorczak A, Madzio J, Lejman M, Sędek Ł, Kowalczyk J, Szczepański T, Młynarski W, Młynarski W, et al: Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion. Oncol Lett 18: 6926-6932, 2019.
APA
Wrona, E., Jakubowska, J., Pawlik, B., Pastorczak, A., Madzio, J., Lejman, M. ... Młynarski, W. (2019). Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion. Oncology Letters, 18, 6926-6932. https://doi.org/10.3892/ol.2019.11046
MLA
Wrona, E., Jakubowska, J., Pawlik, B., Pastorczak, A., Madzio, J., Lejman, M., Sędek, Ł., Kowalczyk, J., Szczepański, T., Młynarski, W."Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion". Oncology Letters 18.6 (2019): 6926-6932.
Chicago
Wrona, E., Jakubowska, J., Pawlik, B., Pastorczak, A., Madzio, J., Lejman, M., Sędek, Ł., Kowalczyk, J., Szczepański, T., Młynarski, W."Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion". Oncology Letters 18, no. 6 (2019): 6926-6932. https://doi.org/10.3892/ol.2019.11046
Copy and paste a formatted citation
x
Spandidos Publications style
Wrona E, Jakubowska J, Pawlik B, Pastorczak A, Madzio J, Lejman M, Sędek Ł, Kowalczyk J, Szczepański T, Młynarski W, Młynarski W, et al: Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion. Oncol Lett 18: 6926-6932, 2019.
APA
Wrona, E., Jakubowska, J., Pawlik, B., Pastorczak, A., Madzio, J., Lejman, M. ... Młynarski, W. (2019). Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion. Oncology Letters, 18, 6926-6932. https://doi.org/10.3892/ol.2019.11046
MLA
Wrona, E., Jakubowska, J., Pawlik, B., Pastorczak, A., Madzio, J., Lejman, M., Sędek, Ł., Kowalczyk, J., Szczepański, T., Młynarski, W."Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion". Oncology Letters 18.6 (2019): 6926-6932.
Chicago
Wrona, E., Jakubowska, J., Pawlik, B., Pastorczak, A., Madzio, J., Lejman, M., Sędek, Ł., Kowalczyk, J., Szczepański, T., Młynarski, W."Gene expression of ASNS, LGMN and CTSB is elevated in a subgroup of childhood BCP‑ALL with PAX5 deletion". Oncology Letters 18, no. 6 (2019): 6926-6932. https://doi.org/10.3892/ol.2019.11046
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