NDLI: The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number

Content Provider	PubMed Central
Author	Gregers, Jannie Christensen, Ib Jarle Dalhoff, Kim Lausen, Birgitte Schroeder, Henrik Steen, Rosthoej Carlsen, Niels Schmiegelow, Kjeld Peterson, Curt
Abstract	The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants (platelet 73 vs 99/105 × 109/L, P = .004, hemoglobin 5.6 vs 5.9/6.0 mmol/L, P = .004) and a higher degree of liver toxicity in patients with RFC GG variant (alanine aminotransferase 167 vs 127/124 U/L, P = .05). In conclusion, the RFC 80G>A polymorphism interacts with chromosome 21 copy numbers and affects both efficacy and toxicity of MTX.
Related Links	http://dx.doi.org/10.1182/blood-2010-01-256958
Ending Page	4677
Page Count	7
Starting Page	4671
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	23
Volume Number	115
Language	English
Publisher	American Society of Hematology
Publisher Date	2010-06-10
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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