LEUKAEMIC SUBCLONES IN CHRONIC MYELOGENOUS LEUKAEMIA

Abstract

Abstract. Serial karyotype studies have been done during cytostatic treatment in a patient with CML in blastic crisis. A course of cytosine arabinoside and thioguanine resulted in a dramatic decrease in the frequency of a 54‐chromosome clone and simultaneous increases of a 46, XY and a 50‐chromosome clone. At the same time the cytological composition of the bone marrow changed towards normal and some temporary clinical improvement took place. Comparison of data on karyotypes and cytology suggest that the highly abnormal karyotypes represented myeloblasts and promyelocytes, whereas early red cell precursors were 46, XY cells. In the discussion the following suggestions are made: (A) Heterogeneity of a leukaemic cell population, as evidenced by differences in karyotypes, may be associated with differences in drug sensitivity. This represents a rationale for multiple drug therapy. (B) Differentiation of leukaemic cells may not be compatible with highly abnormal karyotypes; in turn, lack of differentiation may result in a growth advantage of cells with severe karyotype abnormalities, which would explain the typical evolution of CML from a condition characterized by a single karyotype abnormality (the Ph1‐chromosome) and successful differentiation to a state with multiple karyotype abnormalities and lack of cell differentiation, ending in blastic crisis. (C) It might be possible to postpone the development of blastic crisis if treatment was directed against the developing abnormal clones during the chronic phase of CML. It is proposed to study the use of intermittent intensive chemotherapy in the chronic phase of CML. In a preliminary observation of incipient malignant karyotype evolution in a patient with CML, the secondary karyotype abnormalities almost disappeared after a course of cytosine arabinoside and thioguanine.