Different fusion genes of BCR-ABL1 are all leukemogenic for acute lymphoblastic leukemia or chronic myeloid leukemia (CML). According to results published in Leukemia, the particular transcripts present in patients with CML are correlated with sex and age and are not constant worldwide.
This study systematically assessed the frequency of these leukemogenic fusion genes in patients with CML. Data on 45,503 patients with newly diagnosed CML was provided by 113 centers from Africa, Asia, Europe, Australia, and South America.
The proportion of patients expressing the e13a2 transcript, also called b2a2, was 37.9%. The proportion of patients expressing e14a2, also called b3a2, was 62.1%. This value includes cases in which e13a2 and e14a2 were coexpressed.
The researchers found that e13a2 was more frequently expressed in men, at 39.2%, compared with women, at 36.2% (odds ratio [OR], 1.149; 95% CI, 1.106-1.194; P <.0001). In addition, e13a2 correlated with age. It was expressed in 39.6% of pediatric patients and decreased to 31.6% of patients aged 80 years or older (OR, 0.647; 95% CI, 0.560-0.749; P <.0001). The frequency of e13a2 was not constant worldwide.
Additional rare transcripts were reported in 1.93% of patients (666/34,561). Proportion of rare transcripts correlated with sex, occurring in 2.27% of female patients and in 1.69% of male patients (OR, 1.352; 95% CI, 1.159-1.576; P =.0001). Rare transcript proportion also associated with age, with expression in 1.79% of pediatric patients and in 3.84% of patients aged 80 years or older.
These results suggest that differences in proportions of leukemogenic transcripts might not be random. Because transcript variants can affect prognosis, understanding these patterns could help guide treatment and anticipate treatment outcomes.
However, the authors acknowledged some caveats regarding these results: “The data should be considered with caution, [and] only as a best approximate to the true transcript frequency, because the overview could not cover homogeneously all continents, and the data of rare transcripts were collected mainly from Asia and Europe and were not available across all centers.”
- Baccarani M, Castagnetti F, Gugliotta G, et al. The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview [published online January 23, 2019]. Leukemia. doi:10.1038/s41375-018-0341-4