Clonal changes in chronic granulocytic leukemia in blastic transformation and during remission

Cytogenetic studies of the peripheral blood and marrow of a patient with chronic granulocytic leukemia in blastic transformation revealed the following abnormalities: 1) a Philadelphia chromosome with the usual 9:22 translocation; 2) a three break rearrangement (insertion) of chromosome #11; and 3) a deletion of the short arm in chromosome #16. Clinical and hematologic remission developed after three courses of intermittent chemotherapy with transient but complete bone marrow aplasia. Studies performed during remission revealed two cellular clones. One had the same karyotype already described and the second showed only a Ph1 chromosome. We postulate that the pretreatment clone evolved from Ph1-positive cells in this patient with chronic granulocytic leukemia during a short, undiagnosed stable phase. Treatment allowed the reappearance of the Ph1-positive clone. The second abnormal clone was apparently partially eradicated but normal cells did not repopulate the bone marrow, suggesting that either the Ph1-positive cells were greatly resistant to therapy or that there were no remaining normal myelogenous stem cells. In addition, we found that there have been few reports of abnormalities involving chromosomes #11 and #16, and that an inserting chromosome #11 has never been reported.