CML: Its Cause and Management1,2

� The Bcr-Abl fusion protein, the product of the Ph chromosome, fulfills the criteria for an ideal

molecular target in cancer. Extensive research has shown that Bcr-Abl is the unique

pathophysiologic cause of CML.

� Bcr-Abl tyrosine kinase activity is constitutively increased in CML cells, affecting numerous

signal transduction pathways that are essential for leukemic transformation, including increased cellular proliferation, antiapoptotic effects, and adhesion defects.

� A primary goal of therapy for CML is achieving a complete or major cytogenetic response�

eliminating or substantially reducing Ph+ cells.

� Patients who achieved a complete/major cytogenetic response with stem cell transplantation

(SCT) or interferon-alpha (IFN-α) had prolonged survival vs patients without such a response.

� Longer follow-up is required to determine the survival benefit of Gleevec�.

References

1. Sawyers CL. Chronic myeloid leukemia. N Engl J Med. 1999;340:1330-1340.

2. Giralt S, Kantarjian H, Talpaz M. Treatment of chronic myelogenous leukemia. Semin Oncol.

1995;22:396-404.