Myron Karon

University of Southern California

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Sherman M. Weissman

Yale University

Richard L. Momparler

Centre Hospitalier Universitaire Sainte-Justine

Emil J. Freireich

The University of Texas MD Anderson Cancer Center

William F. Benedict

The University of Texas MD Anderson Cancer Center

Denman Hammond

University of Southern California

Robert E. Hittle

Children's Hospital of Los Angeles

Jerry Z. Finklestein

Children's Cancer Center

David Rigler

Children's Hospital of Los Angeles

Emil Frei

Dana-Farber Cancer Institute

José Antonio Ortega

Universidad Autónoma de Madrid

Cooperative Institutions

University of Southern California

Children's Hospital of Los Angeles

National Institutes of Health

National Cancer Institute

University of California, Los Angeles

University of California, San Francisco

Southern California University for Professional Studies

Cornell University

Anderson Hospital

United States Public Health Service

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Cellular Phosphorylation of 1-β-d-Arabinofuranosylcytosine and 5-Azacytidine with Intact Fibrosarcoma and Leukemic Cells

Cancer Research (1975)

Thomas Lee Myron Karon Richard L. Momparler

The phosphorylation of 1-β-d-arabinofuranosylcytosine (ara-C) and 5-azacytidine (5-aza-C) by A(T1)C1-3 hamster fibrosarcoma cells and L5178Y murine leukemic cells was studied, using intact cells. The cellular phosphorylation of both these nucleoside analogs appears to follow Michaelis-Menton kinetics. The apparent Km value for ara-C in the fibrosarcoma and leukemic cells was about 40 µm, whereas the apparent Km values for 5-aza-C in these cells were about 1.3 and 0.41 mm, respectively. Deoxycytidine and cytidine were found to be potent competitive inhibitors of the phosphorylation of ara-C and 5-aza-C, respectively. ara-C and 5-aza-C were found to be weak competitive inhibitors of the phosphorylation of deoxycytidine and cytidine, respectively. A clone isolated from the fibrosarcoma cells that was partially resistant to the cytotoxic effects of ara-C exhibited a higher Km value for both ara-C and deoxycytidine than the wild-type fibrosarcoma cells.

Cytidine

HT1080

clone (Java method)

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Citations (9)

Application of Immunofluorescence to the Study of Human Leukemia

JNCI Journal of the National Cancer Institute (1964)

Mary Alexander Fink Richard A. Malmgren Frank J. Rauscher Henry C. Orr Myron Karon

The concentrated plasma of individuals with leukemia has been shown by several electron microscopists to contain virus-like particles. In the present study, plasmas containing similar particles were used as an antigen in the production of an antiserum in rabbits. After absorption with normal human antigens and labeling with fluorescein isothiocyanate, this serum reacted specifically with various cellular elements of the bone marrow and peripheral blood of a significant number of patients with leukemia, and failed to react with leukocytes of nonleukemic individuals. A similar antibody prepared against a murine leukemia virus (Rauscher) cross-reacted with the bone marrow and peripheral blood cells from some humans with leukemia, and especially with the cells from a patient with erythroleukemia. It is of interest that this murine leukemia resembles human erythroleukemia pathologically. Tissue culture cells of Burkitt's lymphoma reacted strongly with the antihuman leukemia fluorescent antibody, and less strongly with the antimurine. These same preparations of fluorescent antibody did not react with HeLa cells infected with either Herpes simplex or Herpes zoster viruses. These findings are interpreted as supporting the hypothesis of a viral etiology of human leukemia, and as suggesting a strong probability of antigenic similarities among strains of leukemia virus infecting various species.

Fluorescein isothiocyanate

Immunofluorescence

Direct fluorescent antibody

10.1093/jnci/33.3.581

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Citations (41)

Additive therapy in the maintenance of remission in acute lymphoblastic leukemia of childhood: The effect of the initial leukocyte count

Cancer (1974)

Denis R. Miller Marilyn Sonley Myron Karon Norman E. Breslow Denman Hammond

Following introduction of M1 marrow remission in 81% or 329 of 407 patients treated with prednisone and biweekly intravenous methotrexate, 321 patients were randomly assigned to one of six maintenance treatment regimens designed to evaluate the effect of bimonthly intravenous pulses of the additives actinomycin D, nitrogen mustard, and 5-fluorouracil on the duration of remission in acute lymphoblastic leukemia of childhood. In patients with an initial WBC below 20,000/mm3, a statistically significant beneficial effect of additives was observed in Regimen 1 (actinomycin D with 6MP, nitrogen mustard with methotrexate), Regimen 2 (actinomycin D with 6MP and methotrexate), and Regimen 6 (5-fluorouracil with 6MP and methotrexate). Children with an initial WBC above 20,000/mm3 had the least favorable prognosis; in this group additives appeared to have an adverse effect but the difference was not significant. Survival was also significantly longer in patients with an initial WBC of less than 5000/mm3, when compared to those with an initial WBC of above 20,000/mm3. Little difference in the degree or frequency of hematologic, gastrointestinal, and hepatic toxicity was encountered in the various regimens. These results indicate that additive therapy is beneficial in those patients with the most favorable prognosis and that the prognostic effects of the initial WBC must be given careful consideration in future protocol design, patient randomization, and data analysis of controlled clinical trials.

Regimen

Maintenance therapy

Acute lymphocytic leukemia

10.1002/1097-0142(197409)34:3<508::aid-cncr2820340306>3.0.co;2-t

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Citations (32)

Pseudouridine metabolism. II. Urinary excretion in gout, psoriasis, leukemia, and heterozygous oroticaciduria.

PubMed (1962)

Sherman M. Weissman Arthur Z. Eisen Myron Karon

Pseudouridine

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Citations (35)

Studies on the Pseudouridinuria of Chronic Lymphocytic Leukemia

Blood (1964)

Marvin Lewis Sherman M. Weissman Myron Karon

Pseudouridine

Purine metabolism

Overproduction

Orotic acid

10.1182/blood.v24.5.567.567

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Citations (5)

Chromatid Breakage: Cytosine Arabinoside-Induced Lesions Inhibited by Ultraviolet Irradiation

Science (1971)

William F. Benedict Myron Karon

Exposure to ultraviolet light can reduce the frequency of chromatid breaks induced by cytosine arabinoside in the DNA synthetic and post-DNA synthetic phases of the cell cycle. This effect can be correlated temporally with a decrease in the uptake of tritiated thymidine after ultraviolet treatment, implying that the genesis of such breakage is intimately related to DNA synthesis and that such synthesis is not confined to the DNA synthetic phase.

Cytosine

Thymidine

Ultraviolet

Ultraviolet light

Breakage

10.1126/science.171.3972.680

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Citations (11)

An approach to the molecular basis of the protein synthesis defect in thalassemia

The Journal of Pediatrics (1965)

Myron Karon David Heywood Sherman M. Weissman

Basis (linear algebra)

10.1016/s0022-3476(65)81950-3

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Citations (0)

The effect of 1-beta-D-arabinofuranosylcytosine on macromolecular synthesis in KB spinner cultures.

PubMed (1966)

Myron Karon Patrick H. Henry Sherman M. Weissman Carol Meyer

1-β-d-Arabinofuranosylcytosine inhibited DNA synthesis and cellular proliferation in suspension cultures of KB cells. RNA synthesis and maturation continued normally, as the cells underwent marked enlargement.

BETA (programming language)

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Citations (28)

Virus-Like Particles and Cytopathic Activity in Urine of Patients with Leukemia

Blood (1966)

Richard P. Ames J Sobota Reginald L. Reagan Myron Karon

Cytopathic effect

Feline leukemia virus

10.1182/blood.v28.3.465.465

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Citations (15)