t(8;16)(p11;p13) KAT6A/CREBBP

Review on t(8;16)(p11;p13) KAT6A/CREBBP, with data on clinics, and the genes implicated. Clinics and pathology Disease Acute myeloid leukemia (AML) including AMLM4, AML-M5a/M5b; Treatment related AML (tAML). Note In t-AML with t(8;16), patients often had a previous history of solid tumour (breast cancer) or haematological diseases (CMML, lymphomas). Phenotype/cell stem origin AML with t(8;16) may arise from an early stem cell with myeloid and monoblastic differentiation potential. Epidemiology Rare disease: a hundred and twenty cases have been reported in Mitelman database; (<1% of AML); found in children (median age at diagnosis: 1.2 years) and adults (median age at diagnosis: 59.4 years) with a female predominance (2/3). Clinics Disseminated intra vascular coagulation may be present; extramedullary infiltration; 20% of the cases could be therapy-related. Cytology Blast cells present a myelomonocytic stage of differentiation, and are characterized by a phenomenon of erythrophagocytosis with strong peroxidase and esterase activities. Immunophenotyping reveals CD4, CD14, CD13, CD33, CD56 and HLA-DR positives; CD34, CD117 and CD133 negatives. t(8;16)(p11;p13) Gbanding (left) Courtesy Thomas Smol and Marie-Agnès Collonge-Rame (top), Jean-Luc Lai (second row) and Charles D. Bangs (third and bottom row), Rbanding (right) Courtesy Thomas Smol and MarieAgnès Collonge-Rame (top) and Jean-Luc Lai (second row), and ideogram (bottom right) Courtesy Charles D. Bangs. t(8;16)(p11;p13) KAT6A/CREBBP Smol T, Collonge-Rame MA. Atlas Genet Cytogenet Oncol Haematol. 2015; 19(7) 477 The t(8;16) has been cloned and shown to fuse the MOZ (monocytic leukemia zinc finger) gene at 8p11.2 to the CBP (CREB binding protein) gene at 16p13.3. The MOZ gene has also been found to be involved in variant translocations t(8;19)(p11;q13) and t(8;22)(p11;q13) and inv(8)(p11q13) translocations associated with M5/M4 AML.This translocation is associated with AML M5/M4. In the majority of cases it is associated with features of hemophagocytosis by leukemic cells, particularly erythrophagocytosis Text and iconography Courtesy Georges Flandrin 2001. t(8;16)(p11;p13) : FISH with BAC KAT6A RP11-313J18 (8p11-21) probe (Amplitech) in red and BAC RP11-489O1 (16p13.11) probe (Amplitech) in green Courtesy Thomas Smol and Marie-Agnès Collonge-Rame. t(8;16)(p11;p13) KAT6A/CREBBP Smol T, Collonge-Rame MA. Atlas Genet Cytogenet Oncol Haematol. 2015; 19(7) 478 Blue boxes represent exons of KAT6A gene and orange boxes represent exons of CREBBP gene (diagram is not to scale) Prognosis The prognosis is poor. In published series, death of patients occurs in half of the cases during the first 10 months after diagnosis due to infections or bleeding; survival is often less than 1 year but spontaneous remission has occurred (at least) once.