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

Abstract

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.