phosphorus-radioisotopes and Leukemia--Lymphocytic--Chronic--B-Cell

The use of radioactive phosphorus (32P) to treat the myeloproliferative disorders (chronic leukemia, polycythemia vera and essential thrombocythemia) began in 1939 when John H. Lawrence treated the first patient on the basis of work done in the laboratory animals that found localization of the radioisotope in the spleen, liver, bone and in leukemic cells sufficient to indicate a therapeutic potential. After World War II when 32P became widely available, it was used extensively to treat the chronic leukemias and polycythemia vera. Its use in the treatment of essential thrombocythemia began later in 1950. Today it is not widely used in the treatment of the chronic leukemia, if at all, its use in polycythemia vera appears to have decreased substantially and replaced by hydroxyurea, and its use in the management of essential thrombocythemia is not widespread. In each instance it has been replaced by a drug developed for use in cancer chemotherapy, and in some instances by interferon. It probably has wider use in polycythemia vera in the rest of Western Europe than in the UK, and there are cogent reasons to suggest that it may be the best tool for the treatment of polycythemia vera. Thus have we discarded a treatment modality that in polycythemia vera may be the best?

Topics: Adult; Aged; Alkylating Agents; Chlorambucil; Clinical Trials as Topic; Combined Modality Therapy; Drug Utilization; Humans; Hydroxyurea; Immunologic Factors; Interferons; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Myeloproliferative Disorders; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy; Thrombocythemia, Essential

Following the development of the cyclotron in 1932, radio-isotopes became available for use in medicine both as tracer substances and therapeutic agents. The father of nuclear medicine, Dr J. H. Lawrence, pioneered their use in a range of disease states and found that radio-isotopes were of enormous value in the diagnosis and treatment of haemopoetic disease, particularly the myeloproliferative disorders. Radioactive phosphorus 32P emerged as the radio-isotope of choice for the myelosuppressive treatment of myeloproliferative disorders. This article also describes the use of radio-isotopes in the treatment of other disorders: chronic myeloid leukaemia, chronic lymphocytic leukaemia and myeloma, work that is now largely forgotten. All myeloproliferative disorders may evolve without treatment into myelodysplastic syndrome or blast-cell transformation. It is accepted that life is prolonged in myeloproliferative disorders treated with 32P or alkylating agents, yet both are leukaemogenic. The ideal form of treatment for polycythaemia vera is unknown and will remain so, for patients with this disorder often outlive their physician and achieve 90% of normal life expectation. 32P remains the treatment of choice for elderly patients with polycythaemia vera.

Topics: Animals; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multiple Myeloma; Phosphorus Radioisotopes; Polycythemia Vera

BCR is an interesting signaling protein, whose cellular function is currently unknown. Its biochemical properties include serine kinase activity, SH2-binding activity, and a GTPase-activating activity. The SH2-binding activity is particularly interesting because it may link BCR to signaling pathways involving SH2-containing molecules. Since tyrosine phosphorylation of BCR has been detected in CML-derived cell lines and since tyrosine-phosphorylated BCR shows increased affinity toward certain SH2 domains, it seems particularly important to further characterize this activity. This chapter described a simple purification scheme for partial purification of BCR, which can be used to assess in vitro kinase and SH2-binding activities.

Topics: Adenosine Triphosphate; Animals; Binding Sites; Cell Line; Chromatography, Affinity; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 9; Electrophoresis, Polyacrylamide Gel; Exons; GTP Phosphohydrolases; Humans; Kinetics; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Methionine; Oncogene Proteins; Phosphorus Radioisotopes; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcr; Radioisotope Dilution Technique; Recombinant Proteins; Spodoptera; Sulfur Radioisotopes; Transfection; Translocation, Genetic

Topics: Chlorambucil; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Lymphocytes; Mechlorethamine; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes