Blastic erythrophagocytosis in monocytic AML with translocation t(8;22)

A 72-year-old man was referred with anaemia and thrombocytopenia without peripheral blasts. The haemoglobin level was 88 g/L; platelet count, 23 × 109/L; and leucocyte count, 2.5 × 109/L including 1.4 × 109/L neutrophils. A bone marrow (BM) spread showed signs of dysplasia (karyorrhexis and hypogranularity). BM was infiltrated by 75% of CD4+CD11b+CD14+ large monocytic blasts exhibiting erythrophagocytosis (upper row, morphology images, magnification: objective ×100, May-Grünwald Giemsa stain). High-throughput sequencing identified a complex mutational profile in which pathogenic variants were TET2 c.4824T>G (variant allele frequency [VAF] 55%), TET2 c.2370del (VAF 50%), CDKN2A c.330G>A (VAF 18%), TP53 c.742C>T (VAF 16%), ASXL1 c.3117del (VAF 6%) and RUNX1 c.556C>T (VAF 5%). BM cytogenetic analysis revealed a complex karyotype (six abnormalities) including t(8;22)(p11;q13) (middle row, karyotype, magnification: objective ×63, RHG-banding). The t(8;22) led to a rearrangement between KAT6A (alias MOZ) and EP300 genes mapped on 8p11.21 and 22q13.2 respectively (lower row, dual fusion probe, Sysmex, Kobe, Japan). The t(8;22)(p11;q13), which results in a chimeric MOZ-p300 protein, is a variant of the t(8;16)(p11;p13) where MOZ is fused to CBP. This is the fourth case of MOZ::EP300 rearrangement reported in acute myelomonocytic/monocytic leukaemia, associated with erythrophagocytosis and yielding a poor prognosis, yet liable to targeted therapy. This study was supported by the French Association AHB ‘Association d'hématologie biologique de Tours’ (# W372006363). The patient provided informed consent for the use of the analyses, and the data were anonymized to ensure they could not be identified.