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.
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Authors | S S Matsumoto, A L Yu, L C Bleeker, B Bakay, F H Kung, W L Nyhan |
Journal | Blood
(Blood)
Vol. 60
Issue 5
Pg. 1096-102
(Nov 1982)
ISSN: 0006-4971 [Print] United States |
PMID | 6289941
(Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Deoxyadenine Nucleotides
- Deoxyadenosines
- Pentostatin
- Nucleotidases
- purine 5'-nucleotidase
- Adenosine Deaminase
- Vidarabine
- Thymidine
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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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