Polycomb complexes in MLL-AF9-related leukemias

t(9;11)-Induced leukemia is present both in children and adults, and depending on age, can cause predominantly acute lymphoblastic (ALL) or acute myeloid leukemia (AML), respectively. In general, in infants, it is characterized by poor (ALL) or intermediate (AML) prognosis, whereas in adults, it is classified as being of intermediate-high risk [15,24,31]. Its hallmark is the chromosomal translocation between chromosomes 9 and 11, leading to the formation of the MLL-AF9 fusion gene. The expressed chimeric protein was shown to be crucial for leukemia progression. MLL-AF9 recruits - among other factors - the super elongation complex (SEC), leading to aberrant activation of target genes [4,5,9,17,24]. The Polycomb group of proteins plays crucial roles in many processes, such as embryogenesis, differentiation, and maintaining cell homeostasis, and recently reports linking it to MLL-AF9 have emerged. This review will focus on its role in t(9;11)-related leukemia, highlighting the possible therapeutic-targeting strategies.The work in the Di Croce laboratory is supported by Grants from the Spanish of Economy, Industry and Competitiveness (MEIC) (PID2019-108322GB-100), “Fundación Vencer El Cancer” (VEC), the European Regional Development Fund (ERDF), and from Secretaria d′Universitats i Recerca del Departament d′Economia i Coneixement de la Generalitat de Catalunya (Programa Operatiu FEDER de Catalunya 2014–2020, and from AGAUR. AS is supported by fellowship from “la Caixa” Foundation (ID 100010434)). The fellowship code is LCF/BQ/DI17/11620007. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant agreement no. 713673. We acknowledge support of the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III, and to the EMBL partnership and to the cofinancing with funds from the European Regional Development Fund (FEDER) (Programa Operativo FEDER Plurirregional de España (POPE) 2014–2020); Centro de Excelencia Severo Ochoa; CERCA Programme/Generalitat de Cataluny