Acute myeloid leukemia (AML) in children is still associated with inferior outcome, higher mortality, and relapse rate than the more frequent acute lymphoblastic leukemia (ALL). Non-random chromosomal aberrations are often involved in the development of AML with such poor outcome. One of these aberrations was identified recently in a group of children under the age of 24 months old, named the translocation of t(7;12)(q36;p13) which leads to a gene fusion called MNX1-ETV6 fusion. In pediatric AML initial studies have reported the translocation t(7;12)(q36;p13) to been found in up to 20-30% of the cases, however lower incidence was shown from the Nordic Organization of Pediatric Haematology and Oncology (NOPHO) leukemia registry. Using murine mouse models and human induced pluripotent stem cells (IPSC cells), we recently showed that the ectopic expression of MNX1 in hematopoietic progenitor cells from fetal origin only was able to induce AML, in concordance with the clinical finding that this AML subtype is only found in infants. Furthermore, we also found that MNX1 is associated with methyl transferases and members of methionine cycle leading to important histone modifications, specifically H3K4me3 and H3K27me, which caused aberrant gene expression, genome-wide chromatin modifications and DNA damage. In the current study, we aim to utilize the current advancements in single-cell technologies, our understanding of the molecular mechanism of MNX1, and our IPSC with 3D organoids to develop a pre-clinical therapy model for the t(7;12) patients, that can be progressed to clinical trials.