Resistance mechanisms to methotrexate in tumors

J. R. Bertino, E. Göker, R. Gorlick, W. W. Li, D. Banerjee

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The mechanisms of intrinsic and acquired resistance to methotrexate (MTX) in human tumors are reviewed herein. In blasts from patients with acute lymphocytic leukemia, resistance mechanisms found are decreased uptake and increased dihydrofolate reductase (DHFR) activity. A major cause of intrinsic resistance to MTX in soft tissue sarcoma cells and in acute myelocytic leukemia appears to be a lack of drug retention, due mainly to low levels of polyglutamylation. A novel association between lack of the retinoblastoma protein and intrinsic MTX resistance has been found. This has been attributed to an increase in DHFR activity, due to an increased rate of transcription of this gene, stimulated by an increase in levels of free E2F, not sequestered by hypophosphorylated retinoblastoma protein.

Original languageEnglish (US)
Pages (from-to)223-226
Number of pages4
JournalOncologist
Volume1
Issue number4
StatePublished - 1996
Externally publishedYes

Fingerprint

Methotrexate
Retinoblastoma Protein
Tetrahydrofolate Dehydrogenase
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Sarcoma
Pharmaceutical Preparations
Genes

Keywords

  • Dihydrofolate reductase
  • Drug resistance
  • Folylpolyglutamate synthetase γ-glutamyl hydrolase
  • Leukemia
  • Methotrexate
  • Sarcoma
  • Trimetrexate

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

Bertino, J. R., Göker, E., Gorlick, R., Li, W. W., & Banerjee, D. (1996). Resistance mechanisms to methotrexate in tumors. Oncologist, 1(4), 223-226.

Resistance mechanisms to methotrexate in tumors. / Bertino, J. R.; Göker, E.; Gorlick, R.; Li, W. W.; Banerjee, D.

In: Oncologist, Vol. 1, No. 4, 1996, p. 223-226.

Research output: Contribution to journalArticle

Bertino, JR, Göker, E, Gorlick, R, Li, WW & Banerjee, D 1996, 'Resistance mechanisms to methotrexate in tumors', Oncologist, vol. 1, no. 4, pp. 223-226.
Bertino JR, Göker E, Gorlick R, Li WW, Banerjee D. Resistance mechanisms to methotrexate in tumors. Oncologist. 1996;1(4):223-226.
Bertino, J. R. ; Göker, E. ; Gorlick, R. ; Li, W. W. ; Banerjee, D. / Resistance mechanisms to methotrexate in tumors. In: Oncologist. 1996 ; Vol. 1, No. 4. pp. 223-226.
@article{2f6ee96802664a86a4d0254465eb10c8,
title = "Resistance mechanisms to methotrexate in tumors",
abstract = "The mechanisms of intrinsic and acquired resistance to methotrexate (MTX) in human tumors are reviewed herein. In blasts from patients with acute lymphocytic leukemia, resistance mechanisms found are decreased uptake and increased dihydrofolate reductase (DHFR) activity. A major cause of intrinsic resistance to MTX in soft tissue sarcoma cells and in acute myelocytic leukemia appears to be a lack of drug retention, due mainly to low levels of polyglutamylation. A novel association between lack of the retinoblastoma protein and intrinsic MTX resistance has been found. This has been attributed to an increase in DHFR activity, due to an increased rate of transcription of this gene, stimulated by an increase in levels of free E2F, not sequestered by hypophosphorylated retinoblastoma protein.",
keywords = "Dihydrofolate reductase, Drug resistance, Folylpolyglutamate synthetase γ-glutamyl hydrolase, Leukemia, Methotrexate, Sarcoma, Trimetrexate",
author = "Bertino, {J. R.} and E. G{\"o}ker and R. Gorlick and Li, {W. W.} and D. Banerjee",
year = "1996",
language = "English (US)",
volume = "1",
pages = "223--226",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",
number = "4",

}

TY - JOUR

T1 - Resistance mechanisms to methotrexate in tumors

AU - Bertino, J. R.

AU - Göker, E.

AU - Gorlick, R.

AU - Li, W. W.

AU - Banerjee, D.

PY - 1996

Y1 - 1996

N2 - The mechanisms of intrinsic and acquired resistance to methotrexate (MTX) in human tumors are reviewed herein. In blasts from patients with acute lymphocytic leukemia, resistance mechanisms found are decreased uptake and increased dihydrofolate reductase (DHFR) activity. A major cause of intrinsic resistance to MTX in soft tissue sarcoma cells and in acute myelocytic leukemia appears to be a lack of drug retention, due mainly to low levels of polyglutamylation. A novel association between lack of the retinoblastoma protein and intrinsic MTX resistance has been found. This has been attributed to an increase in DHFR activity, due to an increased rate of transcription of this gene, stimulated by an increase in levels of free E2F, not sequestered by hypophosphorylated retinoblastoma protein.

AB - The mechanisms of intrinsic and acquired resistance to methotrexate (MTX) in human tumors are reviewed herein. In blasts from patients with acute lymphocytic leukemia, resistance mechanisms found are decreased uptake and increased dihydrofolate reductase (DHFR) activity. A major cause of intrinsic resistance to MTX in soft tissue sarcoma cells and in acute myelocytic leukemia appears to be a lack of drug retention, due mainly to low levels of polyglutamylation. A novel association between lack of the retinoblastoma protein and intrinsic MTX resistance has been found. This has been attributed to an increase in DHFR activity, due to an increased rate of transcription of this gene, stimulated by an increase in levels of free E2F, not sequestered by hypophosphorylated retinoblastoma protein.

KW - Dihydrofolate reductase

KW - Drug resistance

KW - Folylpolyglutamate synthetase γ-glutamyl hydrolase

KW - Leukemia

KW - Methotrexate

KW - Sarcoma

KW - Trimetrexate

UR - http://www.scopus.com/inward/record.url?scp=0342434456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342434456&partnerID=8YFLogxK

M3 - Article

VL - 1

SP - 223

EP - 226

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 4

ER -