The translocation t(9;22), a hallmark of chronic mylogenous leukemia (CML), also occurs in about 25% of adults and in about 2-5% of children with acute lymphoblastic leukemia (ALL). At the molecular level, this translocation is associated with different types of BCR/ABL gene rearrangements which are amenable to detection by a variety of molecular genetic techniques permitting highly sensitive monitoring of the disease.
In patients with CML, employment of qualitative molecular techniques is of limited prognostic value, because complete eradication of the BCR/ABL rearranged cell clone might not be a necessary prerequisite for long-lasting remission or even cure. The introduction of quantitative molecular methodologies, particularly those based on quantitative polymerase chain reaction (Q-PCR) opened ways to very sensitive assessment of disease dynamics, and to early prediction of disease progression. In CML patients after bone marrow transplantation or on therapy with interferon, serial Q-PCR analyses allowed detection of progressive disease 1 to 13 months (median 6 months) prior to hematological relapse. These findings provide a rationale for timely initiation of treatment directed against a still relatively small leukemic clone. Recent data obtained by Q-PCR analysis indicate that increase in BCR/ABL expression in the malignant cells precedes clonal proliferation, thus suggesting a different biological and clinical value of assays based on mRNA and DNA analysis.
