Defective Transport as a Mechanism of Acquired Resistance to Methotrexate in Patients With Acute Lymphocytic Leukemia

Overview of attention for article published in Blood, September 1992

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Title	Defective Transport as a Mechanism of Acquired Resistance to Methotrexate in Patients With Acute Lymphocytic Leukemia
Published in	Blood, September 1992
DOI	10.1182/blood.v80.5.1158.1158
Pubmed ID	1381235
Authors	Tanya Trippett, Scott Schlemmer, Yaroslav Elisseyeff, Erdem Goker, Maria Wachter, Peter Steinherz, Charlotte Tan, Elin Berman, Joel E. Wright, Andre Rosowsky, Barry Schweitzer, Joseph R. Bertino
Abstract	Although the mechanisms of resistance to methotrexate (MTX) are known in experimental tumors made resistant to this drug, little information is available regarding acquired resistance to MTX in patients. A competitive displacement assay using the fluorescent lysine analogue of MTX, N-(4-amino-4-deoxy-N10-methylpteroyl)-N epsilon-(4'-fluorescein-thiocarbamyl)-L-lysine (PT430), was developed as a sensitive method of detection of transport resistance to MTX in cell lines, as well as in blast cells from patients with leukemia. Rapid uptake of PT430 at high concentrations (20 mumol/L) in leukemic blasts resulted in achievement of steady-state levels within 2 hours. Subsequent incubation with the folate antagonists, MTX and trimetrexate (TMTX), which differ in the mode of carrier transport, produced characteristic patterns of PT430 displacement. Flow cytometric analysis of the mean fluorescence intensity in the human CCRF-CEM T-cell lymphoblastic leukemia cell line and its MTX-resistant subline clearly identified the presence of transport deficiency in the resistant subline. Analysis of blasts from 17 patients with leukemia, nine with no prior chemotherapy and eight previously treated with chemotherapy, found evidence of MTX transport resistance in two of the four patients who were treated with MTX and considered to be clinically resistant to the drug. The finding that blast cells of some patients with leukemia considered clinically resistant to MTX is due to decreased MTX transport has important implications for clinical use of this drug and for new drug development.

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This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 August 2009.

All research outputs

#10,741,496

of 30,990,086 outputs

Outputs from Blood

#19,980

of 41,993 outputs

Outputs of similar age

#7,939

of 24,003 outputs

Outputs of similar age from Blood

#45

of 141 outputs

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