# USE OF MTAASE DEFICIENCY IN CANCER TREATMENT

> **NIH NIH R01** · EPITOPE, INC. · 1991 · $148,610

## Abstract

DESCRIPTION:  (Adapted from applicant's abstract) The overall purpose of
this project is to understand differences in MTA metabolism between normal
cells and MTAase-deficient (MTAase-) malignant cells and to develop a
rationale for the treatment of MTAase- tumors with a regimen consisting of
methionine restriction and methotrexate.  The applicant recently completed
an analysis of 100 cases of acute leukemia and found that 10 were MTAase-.
The frequency of the enzyme deficiency was particularly high (38%) in
T-cell acute lymphoblastic leukemia (ALL).  He intends to extend these
studies by determining if MTAase deficiency occurs frequently in other
forms of T-cell malignancy such as T-chronic lymphocytic leukemia and
T-cell lymphoma.  In addition, he will use MTAase+ and MTAase- cell lines
to explore the use of methotrexate, a drug which interferes with both
methionine recycling and adenine nucleotide synthesis, for the selective
killing of MTAase- malignant cells in vitro and in vivo.  He will also
determine if the effect of MTX on MTAase-cells is enhanced by concomitant
methionine restriction.  Finally, the applicant intends to purify human
MTAase to homogeneity (a 1000-fold enrichment has already been achieved)
and to use amino acid sequence analysis of this material (plus an
alternative approach in yeast) in an effort to clone the MTAase gene.
Molecular probes generated during this effort will be utilized to determine
the chromosomal location of the structural gene for MTAase and to
characterize the defect causing MTAase deficiency in malignant cells.

## Key facts

- **NIH application ID:** 3175798
- **Project number:** 5R01CA037881-06
- **Recipient organization:** EPITOPE, INC.
- **Principal Investigator:** JOHN H FITCHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $148,610
- **Award type:** 5
- **Project period:** 1986-09-30 → 1993-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175798

## Citation

> US National Institutes of Health, RePORTER application 3175798, USE OF MTAASE DEFICIENCY IN CANCER TREATMENT (5R01CA037881-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175798. Licensed CC0.

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