NEW YORK (Reuters Health) - Subtypes of acute lymphoblastic leukemia (ALL) differ in cellular accumulation of methotrexate, a finding that is influenced by folate pathway gene expression, according to a new report. This may help explain why the drug is either toxic or non-efficacious for certain subtypes.
Dr. William E. Evans, from St. Jude’s Children Research Hospital in Memphis, Tennessee, and colleagues assessed in vivo accumulation of methotrexate in 101 children with ALL. The findings are reported in The Journal of Clinical Investigation for January.
B-lineage ALL subtypes with TEL-AML1 or E2A-PBX1 gene fusions showed much less cellular accumulation of the drug than subtypes lacking these genetic mutations or hyperdiploid ALL, the authors note.
To better understand the reason for these differences in drug accumulation, the investigators used oligonucleotide microarrays to evaluate folate pathway gene expression in leukemic cells from 197 children.
As noted, the ALL subtypes differed in folate pathway gene expression and this appeared to directly affect methotrexate accumulation.
The current findings identify “E2A-PBX1 ALL as a new subtype with low methotrexate accumulation,” the authors state. “To our knowledge, our studies also provide the first evidence of ALL subtype-specific expression patterns for folate pathway genes.”
The investigators are hopeful that these observations could lead to new strategies for overcoming ALL drug resistance.
Source: J Clin Invest 2005;115:110-117. [ Google search on this article ]
MeSH Headings:Genetic Techniques: Investigative Techniques: Leukemia, Lymphocytic, Acute: Gene Expression Profiling: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
