Overexpression of cyclin D1 in accelerated-phase chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a bi- or triphasic disease. Molecular markers distinct for the phase evolution would be clinically helpful. For signaling transformation and proliferation activities in CML, Bcr-Abl is the pivotal protein. As downstream signals of Bcr-Abl , RAS, PI3-K, and Stat 5 may lead to cell cycle progression mediated by increased expression of cyclin Ds. We analyzed copy numbers of bcr-abl and cyclin D1 transcripts by reverse transcription (RT) and competitive PCR titration in bone marrow cells of 20 patients with CML, 10 in chronic phase (CP) and the other 10 in accelerated phase (AP). The level of bcr-abl transcripts in the AP was not significantly higher than that in the CP; in contrast, the level of cyclin D1 transcripts in the AP was significantly higher than that in the CP (p <0.001). Cyclin D1 RNA expression in the CP of CML was also found to have clinical relevance to time to AP transformation. The median time to AP transformation for the CP patients with cyclin D1 transcripts of 1.50 x 10(4)/microg RNA was significantly shorter than that for those with cyclin D1 transcripts < 1.50 x 10(4)/microg RNA (15 vs. 67 months, p=0.0354) although confirmation to conduct in a larger patient group is required. These results suggest that the expression level of cyclin D1 RNA in bone marrow cells is predictive of the phase evolution in CML and may be helpful in treatment decision-making.