Are different types of BCR-ABL1 transcripts associated with different outcomes?

This study examined outcomes in chronic myeloid leukemia (CML) patients with different types of a genetic abnormality known as BCR-ABL1. While patients with the BCR-ABL transcript e14a2 showed better response to treatment, long-term outcomes were similar between groups.

Certain genetic changes in CML can make it more difficult to treat. Some studies have shown that a genetic mutation (abnormal change) known as BCR-ABL1 transcript (gene code) at diagnosis can predict treatment outcomes. There are different types of BCR-ABL1 transcripts including e13a2 and e14a2. It is important to research if these are linked with different prognoses for CML patients.

170 patients with chronic (early) phase CML were included. All patients showed BCR-ABL1 transcript at diagnosis. 33% of patients had e13a2, 55% had e14a2, and 12% of patients had both. All received treatment with the tyrosine kinase inhibitor imatinib (Gleevec). Treatment outcomes were followed for 65 to 86 months.

Treatment response is often measured based on patients showing less abnormal chromosomes (cytogenetic response) or genetic abnormalities (molecular response) in the blood or bone marrow.

Patients with e14a2 showed a significantly better complete cytogenetic response to treatment at 6 months. However, response rates at 12 months were similar between groups. 62% of patients with e13a2, 78% of patients with e14a2, and 79% of patients with both transcripts achieved complete cytogenetic response at 12 months.

At 18 months, major molecular response was achieved in 54% of patients with e13a2. This was significantly higher in patients with e14a2 (69%) and in patients with both transcripts (66%).

Overall survival rates (proportion who have not died from any cause since treatment) were similar between groups. 10-year overall survival rates were 98% for e13a2, 88% for e14a2, and 75% for both transcripts. Having high-risk disease as well as both transcripts reduced chances of survival 10-fold.

This study concluded that patients with the BCR-ABL transcript e14a2 showed better response to imatinib therapy. However, long-term outcomes were similar between patients with e13a2, e14a2, or both.

Larger studies are needed to confirm these early results.