The karyotype of blastic crisis.

The nonrandomness of chromosome clonal evolution in blastic crisis of chronic myeloid leukemia is well established, with three major changes [+8, +Ph, i(17q)] occurring alone or in combination in over 70% of the patients. The chromosome changes observed in different tissues may reveal the origin of the abnormal clones, as well as provide evidence for distinct or common evolution by different cell populations. The significance of the chromosome abnormalities and their relationship to blastic conversion are discussed. In general, chromosome evolution may be considered a rather reliable predictive or diagnostic parameter of blastic crisis but both the nature and the subsequent behavior of abnormal clones appear to be of critical value. As to the clinical/chromosome correlations, a few major points have emerged: the i(17q) aberration is mostly associated with signs of myeloid differentiation of blasts and a marked basophilia; it is mainly observed in the late stage of the disease, but overall median survival of patients with this marker is usually long; more atypical or complex changes usually are associated with a worse prognosis; patients with only a Ph in their blasts may have a longer survival, at least in some cytologic subgroups; and d) the loss of the Y chromosome seems to protect the cell against further clonal evolution. Finally, the relevance of the chromosome changes in the multistage process of blastic conversion is discussed, and the breakpoints of secondary changes recorded so far are reviewed and examined. It appears that certain chromosome regions are more often affected; these might contain genes of critical importance for the final malignant progression. Molecular biology may provide insight, in the future, on the nature and expression of involved genes.