Molecular and clinical investigations in Philadelphia chromosome-negative chronic myelogenous leukemia

We performed molecular studies in five cases of Philadelphia (Ph) translocation-negative chronic myelogenous leukemia (CML). Among the five, one case showed a 7q - anomaly; the remaining four had normal karyotypes. The 5' or 3' breakpoint cluster region (bcr) DNA probes detected rearrangements in two of the five cases. The two cases with bcr rearrangement showed clinical and hematologic manifestations similar to those with Ph-positive CML; for example, basophilia in the peripheral blood and marked hepatosplenomegaly. On the other hand, the three Ph-negative CML cases without bcr rearrangement manifested somewhat different clinical manifestation; that is, they did not respond to busulfan therapy in the chronic phase. Our observations suggest a heterogeneity in Ph-negative CML with at least two subtypes: one with a rearranged bcr gene showing clinical and hematologic features akin to those of CML with a Ph translocation, and the other without such a rearrangement and with a somewhat different clinical feature. Furthermore, the present data point to the possibility of the existence of Ph-negative CML without bcr rearrangement.