We will perform high-resolution chromosome analysis on bone marrow cells from a large series of patients with acute leukemia. A diagnostic, pre-treatment marrow specimen on each patient will be examined with three different high-resolution techniques. The elongated, finely banded chromosomes obtained with the newer procedures allow more precise identification of abnormalities. Detailed karyologic investigations will be done in conjunction with studies on the strucure and expression of various oncogenes in leukemic cells from these patients. We plan to further assess, on the basis of a large series, whether or not most patients with acute leukemia have clonal chromosome defects and whether subtle rearrangements frequently occur. The finely banded chromosomes will be used to identify breakpoints more precisely. The investigation will determine if high-resolution banding analysis can reveal new subgroups of patients characterized by a consistent, subtle chromosome change and distinctive clinicopathologic features. These findings will be important in identifying chromosome sites that may carry genes critical to the normal control of proliferation and differentiation of specific target cells. One long-term objective is to relate chromosome defects to changes in the function and regulation of genes at affected breakpoints. As an initial step we will attempt to associate specific chromosome changes with alterations in the structure and transcription of specific oncogenes. A cell bank will be developed as a source of leukemic cells for future study. Another long-term objective is to find reliable prognostic indicators. Recent evidence suggests that results obtained with different cytogenetic methods may not be comparable. A large number of cells will be carefully examined from each patient which will make it feasible to quantitatively compare the three different high-resolution techniques with respect to: (a) the proportion of abnormal mitoses within individual specimens; and (b) the overall rate of detection of abnormal clones in the patient population. The karyotypic pattern will be correlated with therapeutic response and survival to determine which high-resolution method or combination of methods gives the most accurate indication of prognosis. (K)
