Clonal evolution analyses of a chronic myeloid leukemia patient with hematopoietic stem cell transplantation based on deep sequencing

Background The Philadelphia (Ph) chromosome is the hallmark chromosome aberration in chronic myeloid leukemia (CML), which confers the cancer phenotype of the disease. However, how the Ph chromosome forms and the genetic clonal evolution structure after targeted Ph treatment are still unclear. Methods In this study, we performed genome sequencing and clonal evolution analyses in a series of bone marrow specimens and skin biopsy from a CML patient who had received hematopoietic stem cell transplantation from her sister, then relapsed (lymphoid blast crisis), and received Ph-targeted therapy. Results The Ph chromosome was the “driver” clonal change in the original CML and the relapse. Both the patient and her sister had micro-deletions in the BCR gene region; however, the patient had a frameshift BRIP1 mutation that may account for the malfunctioning homologous recombination DNA repair of the BCR gene region and formation of the Ph chromosome. Conclusion We found that the BCR-ABL1 translocation was the driving force of the patient’s CML and relapse. The malfunctioning double-strand DNA break repair caused by the BRIP1 mutation could be the cause of Ph chromosome formation in the patient.