In:
Blood, American Society of Hematology, Vol. 106, No. 2 ( 2005-07-15), p. 717-720
Abstract:
We studied whether common polymorphisms in genes involved in folate metabolism affect methotrexate (MTX) sensitivity. Ex vivo MTX sensitivity of lymphoblasts obtained from pediatric patients with acute lymphoblastic leukemia (ALL; n = 157) was determined by the in situ thymidylate synthase inhibition assay after either continuous (21 hours; TSI50, cont) or short-term (3 hours; TSI50, short) MTX exposure. DNA was isolated from lymphoblasts obtained from cytospin slides. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR 677C & gt;T, MTHFR 1298A & gt;C), methionine synthase (MTR 2756A & gt;G), methionine synthase reductase (MTRR 66A & gt;G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G & gt;A), serine hydroxymethyl transferase (SHMT1 1420C & gt;T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC 80G & gt;A) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time PCR. Patients with the MTHFR 1298AC variant or the MTRR 66 G-allele showed decreased in vitro MTX sensitivity measured under both test conditions. SHMT1 1420TT homozygotes only showed decreased MTX sensitivity in the TSI50, cont. In conclusion, polymorphisms in the folate-related genes MTHFR, MTRR, and SHMT1 are related to MTX resistance in pediatric patients with ALL. (Blood. 2005;106:717-720)
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2004-12-4941
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2005
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
Permalink