Increased methotrexate polyglutamylation in acute megakaryocytic leukemia (M7) compared to other subtypes of acute myelocytic leukemia

A. Argiris; G. S.A. Longo; R. Gorlick; W. Tong; P. Steinherz; J. R. Bertino

doi:10.1038/sj.leu.2400647

Increased methotrexate polyglutamylation in acute megakaryocytic leukemia (M7) compared to other subtypes of acute myelocytic leukemia

A. Argiris, G. S.A. Longo, R. Gorlick, W. Tong, P. Steinherz, J. R. Bertino

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

14 Scopus citations

Abstract

Acute myelocytic leukemia (AML) is a malignancy that is intrinsically resistant to methotrexate (MTX). AML blasts, when incubated with radiolabeled MTX, form lower amounts of long chain polyglutamates compared to acute lymphocytic leukemia (ALL) blasts, thus providing an explanation for their lack of responsiveness to MTX. Leukemic blasts obtained from two children with acute megakaryocytic leukemia (M7 subtype) when incubated with radiolabeled MTX showed increased accumulation of total as well as long chain MTX polyglutamates, comparable to levels previously demonstrated in another subtype of AML, acute monocytic leukemia (M5), as well as in blasts from patients with pre-B ALL. We suggest that M7-AML patients with blasts showing increased MIX polyglutamylation might benefit from treatment with MTX.

Original language	English (US)
Pages (from-to)	886-889
Number of pages	4
Journal	Leukemia
Volume	11
Issue number	6
DOIs	https://doi.org/10.1038/sj.leu.2400647
State	Published - 1997
Externally published	Yes

Keywords

Acute megakaryocytic leukemia
Acute myelocytic leukemia
Methotrexate
Polyglutamylation

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.leu.2400647

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title = "Increased methotrexate polyglutamylation in acute megakaryocytic leukemia (M7) compared to other subtypes of acute myelocytic leukemia",

abstract = "Acute myelocytic leukemia (AML) is a malignancy that is intrinsically resistant to methotrexate (MTX). AML blasts, when incubated with radiolabeled MTX, form lower amounts of long chain polyglutamates compared to acute lymphocytic leukemia (ALL) blasts, thus providing an explanation for their lack of responsiveness to MTX. Leukemic blasts obtained from two children with acute megakaryocytic leukemia (M7 subtype) when incubated with radiolabeled MTX showed increased accumulation of total as well as long chain MTX polyglutamates, comparable to levels previously demonstrated in another subtype of AML, acute monocytic leukemia (M5), as well as in blasts from patients with pre-B ALL. We suggest that M7-AML patients with blasts showing increased MIX polyglutamylation might benefit from treatment with MTX.",

keywords = "Acute megakaryocytic leukemia, Acute myelocytic leukemia, Methotrexate, Polyglutamylation",

author = "A. Argiris and Longo, {G. S.A.} and R. Gorlick and W. Tong and P. Steinherz and Bertino, {J. R.}",

note = "Funding Information: This work was supported by American Cancer Society Grant No. BC-561C, the Parker-Hughes Foundation, the Charles A Dana Foundation, and Grant No. CA09512 from the National Cancer Institute. RG is the recipient of an ASCO Young Investigator Award. GSAL is the recipient of an American Italian Cancer Foundation Fellowship. JRB is an American Cancer Society Professor.",

year = "1997",

doi = "10.1038/sj.leu.2400647",

language = "English (US)",

volume = "11",

pages = "886--889",

journal = "Leukemia",

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number = "6",

}

TY - JOUR

T1 - Increased methotrexate polyglutamylation in acute megakaryocytic leukemia (M7) compared to other subtypes of acute myelocytic leukemia

AU - Argiris, A.

AU - Longo, G. S.A.

AU - Gorlick, R.

AU - Tong, W.

AU - Steinherz, P.

AU - Bertino, J. R.

N1 - Funding Information: This work was supported by American Cancer Society Grant No. BC-561C, the Parker-Hughes Foundation, the Charles A Dana Foundation, and Grant No. CA09512 from the National Cancer Institute. RG is the recipient of an ASCO Young Investigator Award. GSAL is the recipient of an American Italian Cancer Foundation Fellowship. JRB is an American Cancer Society Professor.

PY - 1997

Y1 - 1997

N2 - Acute myelocytic leukemia (AML) is a malignancy that is intrinsically resistant to methotrexate (MTX). AML blasts, when incubated with radiolabeled MTX, form lower amounts of long chain polyglutamates compared to acute lymphocytic leukemia (ALL) blasts, thus providing an explanation for their lack of responsiveness to MTX. Leukemic blasts obtained from two children with acute megakaryocytic leukemia (M7 subtype) when incubated with radiolabeled MTX showed increased accumulation of total as well as long chain MTX polyglutamates, comparable to levels previously demonstrated in another subtype of AML, acute monocytic leukemia (M5), as well as in blasts from patients with pre-B ALL. We suggest that M7-AML patients with blasts showing increased MIX polyglutamylation might benefit from treatment with MTX.

AB - Acute myelocytic leukemia (AML) is a malignancy that is intrinsically resistant to methotrexate (MTX). AML blasts, when incubated with radiolabeled MTX, form lower amounts of long chain polyglutamates compared to acute lymphocytic leukemia (ALL) blasts, thus providing an explanation for their lack of responsiveness to MTX. Leukemic blasts obtained from two children with acute megakaryocytic leukemia (M7 subtype) when incubated with radiolabeled MTX showed increased accumulation of total as well as long chain MTX polyglutamates, comparable to levels previously demonstrated in another subtype of AML, acute monocytic leukemia (M5), as well as in blasts from patients with pre-B ALL. We suggest that M7-AML patients with blasts showing increased MIX polyglutamylation might benefit from treatment with MTX.

KW - Acute megakaryocytic leukemia

KW - Acute myelocytic leukemia

KW - Methotrexate

KW - Polyglutamylation

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Increased methotrexate polyglutamylation in acute megakaryocytic leukemia (M7) compared to other subtypes of acute myelocytic leukemia

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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