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

  

Authors:	Göker, E.; Lin, J. T.; Trippett, T.; Elisseyeff, Y.; Tong, W. P.; Niedzwiecki, D.; Tan, C.; Steinherz, P.; Schweitzer, B. I.; Bertino, J. R.
Article 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.
Keywords:	adolescent; adult; child; human cell; comparative study; methotrexate; age factors; drug resistance; tumor cells, cultured; acute lymphoblastic leukemia; drug accumulation; drug cytotoxicity; t cell leukemia; in vitro; b cell leukemia; blast cell; polyglutamic acid; leukemia, lymphocytic, acute; human; male; female; priority journal; article; support, non-u.s. gov't
Journal Title:	Leukemia
Volume:	7
Issue:	7
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Date Published:	1993-07-01
Start Page:	1000
End Page:	1004
Language:	English
PUBMED:	7686600
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027317529&partnerID=40&md5=daf4957fffad867a359f48506df950ca
Notes:	Article -- Export Date: 1 March 2019 -- Source: Scopus

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