Usage Information

Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics
Leo Kager, Meyling Cheok, Wenjian Yang, Gianluigi Zaza, Qing Cheng, John C. Panetta, Ching-Hon Pui, James R. Downing, Mary V. Relling, William E. Evans
Leo Kager, Meyling Cheok, Wenjian Yang, Gianluigi Zaza, Qing Cheng, John C. Panetta, Ching-Hon Pui, James R. Downing, Mary V. Relling, William E. Evans
View: Text | PDF | Erratum
Article Oncology

Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics

Abstract

The ability of leukemia cells to accumulate methotrexate polyglutamate (MTXPG) is an important determinant of the antileukemic effects of methotrexate (MTX). We measured in vivo MTXPG accumulation in leukemia cells from 101 children with acute lymphoblastic leukemia (ALL) and established that B-lineage ALL with either TEL-AML1 or E2A-PBX1 gene fusion, or T-lineage ALL, accumulates significantly lower MTXPG compared with B-lineage ALL without these genetic abnormalities or compared with hyperdiploid (fewer than 50 chromosomes) ALL. To elucidate mechanisms underlying these differences in MTXPG accumulation, we used oligonucleotide microarrays to analyze expression of 32 folate pathway genes in diagnostic leukemia cells from 197 children. This revealed ALL subtype–specific patterns of folate pathway gene expression that were significantly related to MTXPG accumulation. We found significantly lower expression of the reduced folate carrier (SLC19A1, an MTX uptake transporter) in E2A-PBX1 ALL, significantly higher expression of breast cancer resistance protein (ABCG2, an MTX efflux transporter) in TEL-AML1 ALL, and lower expression of FPGS (which catalyzes formation of MTXPG) in T-lineage ALL, consistent with lower MTXPG accumulation in these ALL subtypes. These findings reveal distinct mechanisms of subtype-specific differences in MTXPG accumulation and point to new strategies to overcome these potential causes of treatment failure in childhood ALL.

Authors

Leo Kager, Meyling Cheok, Wenjian Yang, Gianluigi Zaza, Qing Cheng, John C. Panetta, Ching-Hon Pui, James R. Downing, Mary V. Relling, William E. Evans

×

Usage data is cumulative from January 2025 through January 2026.

Usage JCI PMC
Text version 1,084 28
PDF 214 8
Figure 203 7
Table 65 0
Supplemental data 33 0
Citation downloads 82 0
Totals 1,681 43
Total Views 1,724
(Click and drag on plot area to zoom in. Click legend items above to toggle)

Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.

Advertisement