Cytogenetic evolution and clonal proliferation in acute transformation of chronic granulocytic leukaemia

Abstract

AMONGST the more important results of chromosome studies in human leukaemias is the occasional demonstration of increasing genetic variation as evidenced by the appearance of a range of cell lines of differing chromosomal constitution. The finding of a variety of cell lines which are not obviously related is common in cases of acute leukaemia and in chronic granulocytic leukaemia at the stage of acute transformation. Only rarely has it been possible by serial study to trace the development of increasing genetic variation and still more rarely to propose any scheme for the interrelationship of the various cell lines. Outstanding exceptions include a case of acute leukaemia studied by Ford and Clarke (1963), a case of chronic granulocytic leukaemia in acute transformation reported by Court Brown and Tough (1963), and a series of cases with chronic granulocytic leukaemia described by de Grouchy and his colleagues (1966).The importance of cases in which the cell lineage can be deduced is that these successive alterations of karyotype may indicate cytogenetic steps essential to the development of increasing malignancy and cellular autonomy. If a pattern can be discerned in these successive changes, it will have implications important for the study of neoplastic disease in general. We have recently studied two cases of chronic granulocytic leukaemia at the stage of acute transformation in which some possible relationships between a range of cell lines may be deduced. CASE REPORTSCase 1 A man, aged 46, presented with clinical and haematological features typical of chronic granulocytic leukaemia. Initial treatment by splenic irradiation was followed by a satisfactory remission which was, however, short-lived. The response to treatment with busulphan was unsatisfactory. Further splenic irradiation led to an incomplete and transient remission, and a second course of busulphan was without beneficial effect. At that time he had severe constitutional symptoms with rapidly progressive splenomegaly and increasing numbers of blast cells and basophils in the peripheral blood. Acute transformation of chronic granulocytic leukaemia was diagnosed 8 months after his initial presentation in the chronic phase of the disease. Treatment with 6-mercaptopurine was followed by a rapid fall in white cell count accompanied by some clinical improvement without

DNA-Flow Cytometry of Blood and Bone Marrow in Chronic Myelogenous Leukemia

“…On the other hand, in patients studied at m alignant m etam orphosis the % Sbm was higher than norm al in 3 out of 4 patients, whereas in 4 out o f 11 patients aneuploidy was noticed at this disease stage. The changes in both proliferation pattern and ploidy level o f hem atopoietic cells in CM L patients at m alignant me tam orphosis, supports the suggestion that this disease phase results from the evolu tion of new clones of neoplastic cells with an apparent growth advantage over nor mal cells and chronic-phase CM L clones [11][12][13]. M oreover, it indicates that flow cytometry is a suitable method for the ear ly diagnosis of m alignant m etam orphosis in CML.…”

Monoclonal Origin of Acute Transformation of Chronic Myelogenous Leukemia

“…Monoclonal origin of chronic myelogenous leukemia has been strongly supported by cytogenetic [5,11] and isoenzymatic studies [4] and it is suggested that karyotype evolutions are frequently, if not all, the cytoge netic basis of acute transformation of chronic myelogenous leukemia [2,7]. In the present case, the greatest interest is whether acute transforma tion might occur in a single clone (45, XO, Ph1 or 46, XY, Ph1 cells) or in both.…”

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

“…The karyotypic investigations also revealed that the Ph chromosome most often was the only identifiable chromosomal change during CP, whereas additional changes frequently accompanied, or even preceded, the acute transformation, in some instances disappearing after treatment, indicating a close relationship between karyotypic evolution and disease progression [22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. Exceptions were noted, however.…”