Chronic myeloid leukaemia in blast phase with t(9;11)(p21;q23), KMT2A::MLLT3 gene fusion

Abstract

Case: A 51-year-old man presented with lymphadenopathy and increasing fatigue. He had been diagnosed with chronic myeloid leukaemia (CML) seven months earlier and had a suboptimal response to first line nilotinib, failing to achieve MR1 with BCR-ABL1/ABL persistently >10% (IS). A repeat bone marrow examination showed 90% blasts, consistent with CML in blast phase (CML-BP). The blasts showed monoblastic morphology and immunophenotype. Conventional karyotype showed both t(9;22)(q34;q11.2), involving the long arm of chromosome 9, and t(9;11)(p21;q23), involving the short arm of the same derivative chromosome 9. FISH confirmed KMT2A breakapart. A core biopsy of cervical lymph node demonstrated a monoblastic leukaemic infiltrate and BCR-ABL1 mutational analysis did not identify any resistance mutations. Discussion: Progression of CML to accelerated or blast phase is usually accompanied by a series of genomic events including BCR-ABL1 resistance mutations, other somatic mutations and additional cytogenetic abnormalities (ACAs). Common ACAs include extra Philadelphia chromosome, trisomy 8, trisomy 9 and isochromosome 17q. KMT2A rearrangement involving the 11q23 locus are common in de novo or therapy related acute leukaemia (both myeloid and lymphoid), but rarely reported in CML blast phase (<1%). The few reported cases show an aggressive clinical presentation, poor outcomes and poor response to tyrosine kinase inhibitors (TKI).