Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia

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Abstract

Summary

The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71 percent of the cases. 9p abnormalities were identified in 26 percent, and monosomy 7 as well as hyperdiploid karyotypes greater than 50 were both found in 17 percent of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58 percent) and an extremely short median remission duration (MRD; 100d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55 percent; MRD 113d). In contrast, all patients with hyperdiploid karyotypes greater than 50 achieved CR, and the overall survival was superior to all other Ph-positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid-associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89 percent) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph-positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph-positive patients has become evident due to variant Ph translocations in 3 percent, and negative PCR assays in 4 percent of the cases.

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