Lack of expression of MTAP in uncommon T-Cell lymphomas

Joseph R. Bertino, Martin Lubin, Nadine Johnson-Farley, Wing C. Chan, Lauri Goodell, Sharathkumar Bhagavathi

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: 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. Patients and Methods: 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. Conclusion: Thus the consequences of MTAP deficiency suggest that new therapeutic interventions for T-cell lymphoma may be feasible.

Original languageEnglish (US)
Pages (from-to)306-309
Number of pages4
JournalClinical Lymphoma, Myeloma and Leukemia
Volume12
Issue number5
DOIs
StatePublished - Oct 2012

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Keywords

  • Methylthioadenosine phosphorylase
  • Peripheral T-cell lymphoma
  • Pralatrexate

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