Chronic myeloid leukemia (CML) was the first hematological malignancy to be associated with a specific genetic lesion. The Philadelphia translocation, producing a BCR-ABL hybrid oncogene, is the most common mechanism of CML development. However, in the present study, b3a2, b2a2 and ela2 fusion junctions of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene were not detected in patients diagnosed with CML three and four years previously. RNA-Seq technology, with an average coverage of ~30-fold, was used to detect gene fusion events in a patient with a 6-year history of CML, identified to be in the chronic phase of the disease. Using deFuse and TopHat-fusion prog... More
Chronic myeloid leukemia (CML) was the first hematological malignancy to be associated with a specific genetic lesion. The Philadelphia translocation, producing a BCR-ABL hybrid oncogene, is the most common mechanism of CML development. However, in the present study, b3a2, b2a2 and ela2 fusion junctions of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene were not detected in patients diagnosed with CML three and four years previously. RNA-Seq technology, with an average coverage of ~30-fold, was used to detect gene fusion events in a patient with a 6-year history of CML, identified to be in the chronic phase of the disease. Using deFuse and TopHat-fusion programs with improved filtering methods, we identified two reliable gene fusions in a blood sample obtained from the CML patient, including extremely low expression levels of the classic BCR-ABL1 gene fusion. In addition, a novel gene fusion involving the ring finger protein 213 (RNF213)-solute carrier family 26, member 11 (SLC26A11) was identified and validated by reverse transcription polymerase chain reaction. Further bioinformatic analysis revealed that specific domains of SLC26A11 were damaged, which may affect the function of sulfate transportation of the normal gene. The present study demonstrated that, in specific cases, alternative gene fusions, besides BCR-ABL, may be associated with the development of CML.
