[Molecular construction of Philadelphia chromosome and its relation to the clinical features].
In 1960, Nowell and Hungerford found, for the first time, a minute chromosome at the metaphase in chronic myelocytic leukemia (CML) cells, which was called Philadelphia chromosome (Ph1 chromosome) later. Ph1 chromosome was considered to be specific for the disease and was frequently used as an important marker for the definite diagnosis. However, in mid-1970s, some cases with acute lymphocytic leukemia (ALL) were also found to have Ph1 chromosome in the leukemic cells. Therefore, Ph1 chromosome seemed to be non-specific for the diagnosis of CML. In 1980s, molecular-biology techniques were applied in the fields of leukemia research. As a result, clear differences were demonstrated between the two diseases (CML and ALL with Ph1 chromosome, respectively) at the molecular level using oncogene concept. In this review, molecular-genetic constructions of ABL, BCR and BCR-ABL hybrid genes in CML, as well as m-BCR-ABL hybrid gene in Ph1 positive ALL are focused in detail. Relationship between these molecular-genetic changes with the clinical features and the mechanism of cell growth in these cells with BCR-ABL or m-BCR-ABL hybrid genes are also discussed.
Kamada
N
N
Research Institute for Nuclear Medicine and Biology, Hiroshima University.
Tanaka
K
K
Asou
H
H
D002873:Chromosome Fragility; D016313:Genes, abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D015394:Molecular Structure; D005810:Multigene Family; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics