Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease

Erdem Göker; James T. Lin; Tanya Trippett; Yaroslav Elisseyeff; William P. Tong; Donna Niedzwiecki; Charlotte Tan; Peter Steinherz; Barry I. Schweitzer; Joseph R. Bertino

Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease

Erdem Göker, James T. Lin, Tanya Trippett, Yaroslav Elisseyeff, William P. Tong, Donna Niedzwiecki, Charlotte Tan, Peter Steinherz, Barry I. Schweitzer, Joseph R. Bertino

Cancer Systems Imaging

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate formation in adult patients might be a contributing cause to the known difference in clinical outcome, since MTX is a key drug in chemotherapy regimens. Adult B-lineage cell ALL blasts and blasts from the patients with T-lineage cell ALL accumulated lower amounts of total MTX and polyglutamates, especially long-chain MTX polyglutamates (glu_3-6) than pediatric B-lineage cell ALL blasts. In view of the importance of polyglutamylation of MTX as a determinant of cytotoxicity of this drug, decreased formation of MTX polyglutamates is likely a contributing cause to the lower cure rate in adult ALL and T-lineage cell ALL as compared to childhood B-lineage cell ALL.

Original language	English (US)
Pages (from-to)	1000-1004
Number of pages	5
Journal	Leukemia
Volume	7
Issue number	7
State	Published - Jul 1993

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

Cite this

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title = "Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease",

abstract = "We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate formation in adult patients might be a contributing cause to the known difference in clinical outcome, since MTX is a key drug in chemotherapy regimens. Adult B-lineage cell ALL blasts and blasts from the patients with T-lineage cell ALL accumulated lower amounts of total MTX and polyglutamates, especially long-chain MTX polyglutamates (glu3-6) than pediatric B-lineage cell ALL blasts. In view of the importance of polyglutamylation of MTX as a determinant of cytotoxicity of this drug, decreased formation of MTX polyglutamates is likely a contributing cause to the lower cure rate in adult ALL and T-lineage cell ALL as compared to childhood B-lineage cell ALL.",

author = "Erdem G{\"o}ker and Lin, {James T.} and Tanya Trippett and Yaroslav Elisseyeff and Tong, {William P.} and Donna Niedzwiecki and Charlotte Tan and Peter Steinherz and Schweitzer, {Barry I.} and Bertino, {Joseph R.}",

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T1 - Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease

AU - Göker, Erdem

AU - Lin, James T.

AU - Trippett, Tanya

AU - Elisseyeff, Yaroslav

AU - Tong, William P.

AU - Niedzwiecki, Donna

AU - Tan, Charlotte

AU - Steinherz, Peter

AU - Schweitzer, Barry I.

AU - Bertino, Joseph R.

PY - 1993/7

Y1 - 1993/7

N2 - We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate formation in adult patients might be a contributing cause to the known difference in clinical outcome, since MTX is a key drug in chemotherapy regimens. Adult B-lineage cell ALL blasts and blasts from the patients with T-lineage cell ALL accumulated lower amounts of total MTX and polyglutamates, especially long-chain MTX polyglutamates (glu3-6) than pediatric B-lineage cell ALL blasts. In view of the importance of polyglutamylation of MTX as a determinant of cytotoxicity of this drug, decreased formation of MTX polyglutamates is likely a contributing cause to the lower cure rate in adult ALL and T-lineage cell ALL as compared to childhood B-lineage cell ALL.

AB - We compared blast cells from adult and pediatric patients with untreated acute lymphoblastic leukemia (ALL) (as separated groups of T-lineage cell and B-lineage cell ALL) to determine if methotrexate (MTX) polyglutamate formation in adult patients might be a contributing cause to the known difference in clinical outcome, since MTX is a key drug in chemotherapy regimens. Adult B-lineage cell ALL blasts and blasts from the patients with T-lineage cell ALL accumulated lower amounts of total MTX and polyglutamates, especially long-chain MTX polyglutamates (glu3-6) than pediatric B-lineage cell ALL blasts. In view of the importance of polyglutamylation of MTX as a determinant of cytotoxicity of this drug, decreased formation of MTX polyglutamates is likely a contributing cause to the lower cure rate in adult ALL and T-lineage cell ALL as compared to childhood B-lineage cell ALL.

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Decreased polyglutamylation of methotrexate in acute lymphoblastic leukemia blasts in adults compared to children with this disease

Abstract

ASJC Scopus subject areas

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