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