Purpose To investigate the effectiveness of a combination\nof 6-thioguanine (6-TG) and pralatrexate (PDX) in methylthioadenosine\nphosphorylase (MTAP)-deficient T-cell acute\nlymphoblastic leukemia (T-cell ALL).\nMethods CCRF-CEM (MTAP?/?) and Molt4 (MTAP+/+)\nT-cell ALL cell lines were treated with 6-TG or PDX and\nevaluated for efficacy 72 h later. NOD/SCID gamma mice\nbearing CEM or Molt4 xenografts were treated with 6-TG\nand PDX alone or in combination to evaluate antitumor\neffects.\nResults CEM cells were more sensitive to 6-TG and PDX\nin vitro than Molt4. In vivo, CEM cells were very sensitive\nto PDX and 6-TG, whereas Molt4 cells were highly\nresistant to 6-TG. A well-tolerated combination of PDX\nand 6-TG achieved significant tumor regression in CEM\nxenografts.\nConclusions The loss of MTAP expression may be therapeutically\nexploited in T-cell ALL. The combination of\n6-TG and PDX, with the inclusion of leucovorin rescue,\nallows for a safe and effective regimen in MTAP-deficient\nT-cell ALL.
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