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Biochemical correlates of the differential sensitivity of subtypes of human leukemia to deoxyadenosine and deoxycoformycin.

Abstract
Leukemic cells incubated in vitro with 2'-deoxyadenosine (dAdo) plus an inhibitor of adenosine deaminase, 2'-deoxy-coformycin (DCF), show different metabolic responses depending on the histologic and immunologic type of the leukemia. Leukemic cells were obtained from 54 patients with acute lymphoblastic leukemia (ALL), 9 with myeloid or nonlymphoblastic leukemia, 3 with chronic lymphocytic leukemia (CLL), and 3 with lymphoma. There was a wide variation in the LD50, the concentration of dAdo that caused 50% inhibition of the incorporation of 3H-thymidine into cells in the presence of 20 microM DCF. T-cell leukemia specimens were much more sensitive to dAdo than were specimens of pre-B-ALL and null-ALL. In leukemic cells that had been incubated with 14C-dAdo plus DCF, a good correlation was observed between the LD50 and the ratio of 14C-deoxyATP to ATP (correlation coefficient for the fit to a hyperbola = 0.853). The accumulation of deoxyATP by the leukemic cell specimens was correlated best with the activity of ecto-ATPase, less well with cytoplasmic 5'-nucleotidase and deoxyadenosine kinase, and poorly with adenosine deaminase and ecto-5'-nucleotidase. The clinical response to DCF therapy of a patient with T-ALL and another with pre-B-ALL was consistent with the in vitro metabolic response of their cells to DCF and dAdo.
AuthorsS S Matsumoto, A L Yu, L C Bleeker, B Bakay, F H Kung, W L Nyhan
JournalBlood (Blood) Vol. 60 Issue 5 Pg. 1096-102 (Nov 1982) ISSN: 0006-4971 [Print] United States
PMID6289941 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Deoxyadenine Nucleotides
  • Deoxyadenosines
  • Pentostatin
  • Nucleotidases
  • purine 5'-nucleotidase
  • Adenosine Deaminase
  • Vidarabine
  • Thymidine
Topics
  • Adenosine Deaminase (metabolism)
  • Adolescent
  • Deoxyadenine Nucleotides (biosynthesis)
  • Deoxyadenosines (pharmacology)
  • Humans
  • Leukemia (metabolism)
  • Leukemia, Lymphoid (metabolism)
  • Leukemia, Myeloid (metabolism)
  • Leukemia, Myeloid, Acute (metabolism)
  • Leukocytes (drug effects)
  • Lymphocytes (drug effects)
  • Lymphoma (metabolism)
  • Male
  • Nucleotidases (metabolism)
  • Pentostatin
  • Thymidine (metabolism)
  • Vidarabine (analogs & derivatives, pharmacology)

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