Journal article
Lack of Expression of MTAP in Uncommon T-Cell Lymphomas
Clinical lymphoma, myeloma and leukemia, Vol.12(5), pp.306-309
10/2012
DOI: 10.1016/j.clml.2012.07.001
PMID: 23040436
Abstract
The majority of peripheral T-cell lymphomas were found to lack methylthioadenosine phosphorylase, an enzyme that is essential for the salvage of adenine from methylthioadenosine, a product of polyamine synthesis. Importantly, tumors that lack this enzyme have been shown to be more sensitive to inhibitors of de novo purine synthesis (6-thioguanine, methotrexate).
T-cell lymphomas, in particular peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL), have only limited and noncurative treatment options.
We report here that a high percentage of PTCL, AITL, and ALCL lack the enzyme methylthioadenosine phosphorylase (MTAP), as do T-cell leukemia and T-cell lymphoblastic leukemia. MTAP-deficient cells cannot cleave endogenous methylthioadenosine to adenine and 5-methylthioribose-1-phosphate, a precursor of methionine, and as a result have enhanced sensitivity to inhibitors of de novo purine biosynthesis. A recently introduced antifolate, pralatrexate, which has been shown to inhibit de novo purine biosynthesis, has been approved for treatment of PTCL and may have an increasing role in therapy. An alternative strategy involving coadministration of methylthioadenosine and high-dose 6-thioguanine has been proposed and may prove to be selectively toxic to MTAP-deficient uncommon lymphomas.
Thus the consequences of MTAP deficiency suggest that new therapeutic interventions for T-cell lymphoma may be feasible.
Details
- Title: Subtitle
- Lack of Expression of MTAP in Uncommon T-Cell Lymphomas
- Creators
- Joseph R Bertino - Departments of Medicine, Pharmacology, and Pathology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJMartin Lubin - Geisel School of Medicine at Dartmouth, Hanover, NHNadine Johnson-Farley - Departments of Medicine, Pharmacology, and Pathology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJWing C Chan - Department of Pathology, University of Nebraska School of Medicine, Omaha, NELauri Goodell - Departments of Medicine, Pharmacology, and Pathology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJSharathkumar Bhagavathi - Departments of Medicine, Pharmacology, and Pathology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ
- Resource Type
- Journal article
- Publication Details
- Clinical lymphoma, myeloma and leukemia, Vol.12(5), pp.306-309
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.clml.2012.07.001
- PMID
- 23040436
- ISSN
- 2152-2650
- eISSN
- 2152-2669
- Language
- English
- Date published
- 10/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984047657202771
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