Purine degradative enzymes in circulating malignant cells of patients with chronic B cell neoplasia

Abstract

Previous reports have shown that the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and ecto-5'-nucleotidase (5'NT), play an important role in the normal development of lymphocytes and that investigations of these enzymes are of value in defining subsets of lymphoid malignancies of T-cell origin. Pharmacological inhibition of one of these enzymes has been found to be an effective treatment for a few lymphatic neoplasia. We have studied the activities of the above enzymes in the circulating malignant cells of 25 patients with B-chronic lymphatic leukemia (B-CLL), four patients with B prolymphocytic leukemia (PLL), seven patients with leukemic centrocytic lymphoma (CC), 18 patients with hairy cell leukemia (HCL) and 16 patients with immunocytoma (IC). For comparison, the blasts of nine patients with 'common' acute lymphatic leukemia (cALL) and normal T (n = 12) and B (n = 8) cells were simultaneously investigated. Despite morphologic similarity, the leukemic cells of the chronic B cell malignancies demonstrate different enzyme patterns. B-CLL is characterized by very low activities of all the enzymes ADA, PNP and 5'NT. In the cells of HCL the highest values of PNP are found. The leukemic cells of IC are characterized by low levels of ADA but moderate levels of PNP and high levels of 5'NT. Thus some of the entities of B malignancies show typical enzyme patterns which might be of importance in defining maturation stages of the disease. The differences in these enzyme patterns can also be made use of in therapy with enzyme inhibitors such as deoxycoformycin.

Surface expression of adenosine deaminase in mitogen-stimulated lymphocytes

“…For each of these stages a precise level of ADA and 5'-nucleotidase, among other enzymes, occurs [25]. It is clear, not only for T cell-derived leukaemias but for most types of haematological malignancies, that the level of purine degradative enzymes is useful for the diagnosis and/or prognosis of the disease [1,[26][27][28]. Finally, an interesting possibility that should be further explored is that purine metabolizing enzymes present on the surface of the cells may be important accessory molecules for cell triggering.…”

5′ nucleotidase in chronic b cell leukemias: A cytochemical and ultrastructural study

“…These studies showed very low levels of enzyme activity in chronic B lymphocytic leukemia (B-CLL) cells [2, 8,. Furthermore 5' NT expression in lymphoproliferative disorders could be related to the hypothetical maturation stage reached by the disorder, as defined by immunological marker studies [17,18].…”