title: Chromatographic forms of terminal deoxynucleotidyl transferase in normal lymphoid cells and in leukemia cells at presentation and relapse.
abstract: Normal thymocyte and bone marrow terminal deoxynucleotidyl transferase (TdT) have distinguishing characteristics by phosphocellulose chromatography in Tris buffer: marrow TdT elutes as a single peak at 0.3 M salt, whereas thymocyte TdT separates into two forms, one at 0.3 M salt and one at 0.4 M salt. Since the majority of TdT-positive acute leukemias are anatomically bone marrow-derived, one would have predicted the presence of a bone marrow TdT-phosphocellulose chromatographic pattern in such patients. However, in 376 consecutive, untreated TdT-positive acute lymphoblastic leukemias (ALL) studied by us we have invariably encountered the two-peak thymocyte-type phosphocellulose pattern. The TdT patterns in the thymic-dependent, TdT-positive lymphoma of AKR mice, and the TdT-positive bone marrow-derived, thymic-independent Abelson virus leukemia of Balb/C mice duplicate the situation in human ALL: a thymocyte pattern is seen in both the marrow-derived and thymus-derived diseases. This chromatographic difference between leukemia-associated and normal marrow-associated TdT in both murine and human leukemia suggested that phosphocellulose-TdT patterns might be useful for monitoring residual marrow tumour cell burden in TdT-positive leukemia. This has not turned out to be the case: in eight patients studied in early relapse the blast cell TdT pattern was the single-peak 0.3 M species. Therefore, leukemic cell TdT cannot reliably be distinguished from normal marrow cell TdT. The chromatographic behaviour of TdT may be regulated by phosphorylation-dephosphorylation, the 0.3 M salt peak can be converted to the 0.4 M salt species by treatment with protein kinase and ATP, and the 0.4 M species can be converted to the 0.3 M form by exposure to alkaline phosphatase. Thus, apparently anatomic compartment-specific forms of TdT may only reflect differing cellular metabolic activity.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001853:Bone Marrow / Q000201:enzymology; D002648:Child; D002675:Child, Preschool; D002852:Chromatography, Ion Exchange; D004253:DNA Nucleotidylexotransferase / Q000032:analysis*; D004254:DNA Nucleotidyltransferases / Q000032:analysis*; D006801:Humans; D007942:Leukemia, Experimental / Q000201:enzymology; D007945:Leukemia, Lymphoid / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology*; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008875:Middle Aged; D013601:T-Lymphocytes / Q000201:enzymology
chemical_list: D004254:DNA Nucleotidyltransferases; D004253:DNA Nucleotidylexotransferase