[Molecular basis of chronic granulocytic leukemia: from test-tube to patient].
BCR/ABL tyrosine kinases are encoded by hybrid oncogene bcr/abl which is a result of t(9;22) reciprocal translocation. Bcr/abl oncogene is located on Philadelphia chromosome which is detectable in hematopoietic cells of more than 95% of patients with chronic myelogenous leukemia, and in some cases of acute lymphocytic leukemia (20-35%) and acute myeloblastic leukemia (5%). Because BCR/ABL tyrosine kinase is localized in the cytoplasm, cooperation with other cytoplasmic and nuclear molecules is necessary for the induction of leukemia. Identification of the molecular mechanisms involved in transduction of the oncogenic signal is likely to be useful in elucidating the molecular mechanisms of leukemogenesis and may eventually lead to the identification of novel targets for antileukemia therapy. One of the possible treatment--inhibition of bcr/abl oncogene expression by antisense strategy--is described below.
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Uniwersytet Thomasa Jeffersona, Instytut Rakowy Jeffersona, Filadelfia, Pennsylvania.
D000818:Animals; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction
D016376:Oligonucleotides, Antisense; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl
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