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  • Title: Lymphoid blast crisis during complete cytogenetic remission following interferon-alpha and hydroxyurea therapy.
    Author: Bose S, Chowdhry VP, Saxena R, Kucheria K.
    Journal: Acta Haematol; 1997; 98(3):155-9. PubMed ID: 9352747.
    Abstract:
    Chronic myelogenous leukemia (CML) is a clonal disorder starting with a chronic phase and progressing to an acute blastic phase. Philadelphia (Ph) chromosome formation results in the relocation of the ABL oncogene from the chromosome 9q34 to BCR region on 22q11, forming the BCR/ABL fusion gene. The Ph chromosome once detected rarely disappears, except as a result of therapy. We present an unusual Ph-positive CML case, which developed lymphoid blast crisis in complete cytogenetic remission following interferon-alpha and hydroxyurea therapy. Sequential cytogenetic investigations were carried out on bone marrow. After a standard Ph translocation seen at diagnosis, from the 8th month of therapy all metaphases showed a normal diploid karyotype. Fluorescence in situ hybridization detected residual BCR/ABL-positive interphase cells during the 12th month of therapy. In the 14th month, the patient showed 27% blasts in marrow though normal cytogenetics was maintained. Present findings suggest blastic transformation occurred in a Ph-negative lymphoid clone. This supports the hypothesis that an actual leukemogenic event occurs in a multipotent stem cell prior to the acquisition of Ph translocation.
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