Chronic myeloid leukaemia (CML) is consistently associated with the BCR-ABL1 fusion gene located on the derivative chromosome 22 (Philadelphia chromosome, Ph + ve) as a result of a t(9;22)(q34;q11.2) translocation. We describe a 36-year-old male in blast phase CML presenting with acute myelomonocytic leukaemia and eosinophilia. Five months after initial disease diagnosis and despite being treated with standard imatinib therapy (400 mg daily) conventional cytogenetic analysis (CCA) demonstrated the evolution of a chromosome 16 pericentric inversion (inv(16)(p13q22)) within the already Ph + ve cells. Bone marrow aspiration and biopsy revealed 60% blasts, positive for CD34, HLADR, CD33 and CD13. Fluorescence in situ hybridization (FISH) and reverse transcription–polymerase chain reaction (RT-PCR) confirmed presence of a CBFβ-MHY11 rearrangement whilst next generation sequencing (NGS) detected an E255K point mutation within the BCR-ABL1 tyrosine kinase domain. Neither the CBFβ-MHY11 rearrangement nor the E225K point mutation were present at diagnosis. The patient received a combination of daunorubicin (60 mg/m2) and cytarabine (100 mg/m2) and had his tyrosine kinase inhibitor (TKI) changed to nilotinib before undergoing a male unrelated donor (MUD) stem cell transplant (SCT). The t(9;22) and inv(16) rearrangements persisted at day 100 post MUD SCT and his TKI was further switched to dasatinib. The patient presented with pleural effusions and had subsequent CNS relapse and passed away from relapsed disease and infective complications, 19-month post MUD allograft.
- Blast phase
- Chronic myeloid leukaemia
- Conventional cytogenetic analysis
- Next generation sequencing
ASJC Scopus subject areas
- Pathology and Forensic Medicine