Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia

Wendy A G Stams; Monique L den Boer; Amy Holleman; Inge M Appel; H Berna Beverloo; Elisabeth R van Wering; Gritta E Janka-Schaub; William E Evans; Rob Pieters

doi:10.1182/blood-2004-10-3892

Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia

Wendy A G Stams, Monique L den Boer, Amy Holleman, Inge M Appel, H Berna Beverloo, Elisabeth R van Wering, Gritta E Janka-Schaub, William E Evans, Rob Pieters

Research output: Contribution to journal › Article › peer-review

77 Citations (Scopus)

Abstract

Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL.

Original language	English
Pages (from-to)	4223-5
Number of pages	3
Journal	Blood
Volume	105
Issue number	11
DOIs	https://doi.org/10.1182/blood-2004-10-3892
Publication status	Published - 1 Jun 2005
Externally published	Yes

Keywords

Asparaginase/therapeutic use
Aspartate-Ammonia Ligase/analysis
Burkitt Lymphoma/drug therapy
Child
Core Binding Factor Alpha 2 Subunit
Disease-Free Survival
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Oligonucleotide Array Sequence Analysis
Oncogene Proteins, Fusion/analysis
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
Prognosis
Recurrence

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10.1182/blood-2004-10-3892

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Stams, W. A. G., den Boer, M. L., Holleman, A., Appel, I. M., Beverloo, H. B., van Wering, E. R., Janka-Schaub, G. E., Evans, W. E., & Pieters, R. (2005). Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia. Blood, 105(11), 4223-5. https://doi.org/10.1182/blood-2004-10-3892

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title = "Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia",

abstract = "Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL.",

keywords = "Asparaginase/therapeutic use, Aspartate-Ammonia Ligase/analysis, Burkitt Lymphoma/drug therapy, Child, Core Binding Factor Alpha 2 Subunit, Disease-Free Survival, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Humans, Oligonucleotide Array Sequence Analysis, Oncogene Proteins, Fusion/analysis, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Prognosis, Recurrence",

author = "Stams, {Wendy A G} and {den Boer}, {Monique L} and Amy Holleman and Appel, {Inge M} and Beverloo, {H Berna} and {van Wering}, {Elisabeth R} and Janka-Schaub, {Gritta E} and Evans, {William E} and Rob Pieters",

year = "2005",

month = jun,

day = "1",

doi = "10.1182/blood-2004-10-3892",

language = "English",

volume = "105",

pages = "4223--5",

journal = "Blood",

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T1 - Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia

AU - Stams, Wendy A G

AU - den Boer, Monique L

AU - Holleman, Amy

AU - Appel, Inge M

AU - Beverloo, H Berna

AU - van Wering, Elisabeth R

AU - Janka-Schaub, Gritta E

AU - Evans, William E

AU - Pieters, Rob

PY - 2005/6/1

Y1 - 2005/6/1

N2 - Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL.

AB - Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL.

KW - Asparaginase/therapeutic use

KW - Aspartate-Ammonia Ligase/analysis

KW - Burkitt Lymphoma/drug therapy

KW - Child

KW - Core Binding Factor Alpha 2 Subunit

KW - Disease-Free Survival

KW - Drug Resistance, Neoplasm

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Oligonucleotide Array Sequence Analysis

KW - Oncogene Proteins, Fusion/analysis

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy

KW - Prognosis

KW - Recurrence

UR - http://www.scopus.com/inward/record.url?scp=19344377657&partnerID=8YFLogxK

U2 - 10.1182/blood-2004-10-3892

DO - 10.1182/blood-2004-10-3892

M3 - Article

C2 - 15718422

SN - 0006-4971

VL - 105

SP - 4223

EP - 4225

JO - Blood

JF - Blood

IS - 11

ER -

Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia

Abstract

Keywords

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