Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors

J. H. Fitchen, Michael Riscoe, B. W. Dana, H. J. Lawrence, A. J. Ferro

Research output: Contribution to journalArticle

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Abstract

5-Methylthioadenosine (MTA) is a naturally occurring nucleoside which is degraded by MTA phosphorylase (MTAase) to adenine and methylthioribose-1-phosphate in all normal mammalian cells. These products of the phosphorylytic cleavage of MTA are recycled to the nucleotide pool and methionine, respectively. Thus, supplemented MTA could theoretically be utilized by MTAase-containing cells as a source of methionine and adenine. In fact, in vitro experiments have shown that MTAase-containing cells proliferate normally in methionine-free medium if MTA is added to the cultures (M.K. Riscoe and A.J. Ferro, J. Biol. Chem., 259:5465-5471, 1984). In contrast, MTAase-deficient malignant cell lines do not proliferate under these conditions. In light of these observations and the recent demonstration (N. Kamatani et al., Blood, 60:1387-1391, 1982) that a proportion of acute lymphoblastic leukemias lack MTAase, we wished to determined if this enzyme deficiency occurs in a variety of human neoplasms. Accordingly, malignant cells from eight patients with acute nonlymphocytic leukemia and ten patients with various solid tumors were assayed for MTAase activity. Samples from one of the eight acute nonlymphocytic leukemia patients and three of the 10 solid tumor patients (one with melanoma, one with squamous cell lung cancer, and one with adenocarcinoma of the rectum) had undetectable MTAase activity. In contrast, erythrocytes, neurtrophils, and monocytes isolated from normal subjects and from patients with immunodeficiency syndromes or cancer all contained enzyme activity. In addition, the methods of preservation, storage, and cell disruption did not affect MTAase activity. These observations confirm and extend the findings of Kamatani et al. (Blood, 60: 1387-1391, 1982) by demonstrating that MTAase deficiency occurs in a variety of human malignancies including acute nonlymphocytic leukemia and solid tumors. This metabolic difference between normal and malignant cells may be therapeutically exploitable.

Original languageEnglish (US)
Pages (from-to)5409-5412
Number of pages4
JournalCancer Research
Volume46
Issue number10
StatePublished - 1986

Fingerprint

Pemetrexed
Phosphorylases
Leukemia
Neoplasms
Acute Myeloid Leukemia
Methionine
Adenine
Squamous Cell Neoplasms
5'-methylthioadenosine phosphorylase
Enzymes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Nucleosides
Rectum
Monocytes
Melanoma
Lung Neoplasms
Adenocarcinoma
Nucleotides
Erythrocytes
Phosphates

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fitchen, J. H., Riscoe, M., Dana, B. W., Lawrence, H. J., & Ferro, A. J. (1986). Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors. Cancer Research, 46(10), 5409-5412.

Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors. / Fitchen, J. H.; Riscoe, Michael; Dana, B. W.; Lawrence, H. J.; Ferro, A. J.

In: Cancer Research, Vol. 46, No. 10, 1986, p. 5409-5412.

Research output: Contribution to journalArticle

Fitchen, JH, Riscoe, M, Dana, BW, Lawrence, HJ & Ferro, AJ 1986, 'Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors', Cancer Research, vol. 46, no. 10, pp. 5409-5412.
Fitchen JH, Riscoe M, Dana BW, Lawrence HJ, Ferro AJ. Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors. Cancer Research. 1986;46(10):5409-5412.
Fitchen, J. H. ; Riscoe, Michael ; Dana, B. W. ; Lawrence, H. J. ; Ferro, A. J. / Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors. In: Cancer Research. 1986 ; Vol. 46, No. 10. pp. 5409-5412.
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