ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/009/SRR5687229/SRR5687229_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/006/SRR5687226/SRR5687226_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/005/SRR5687225/SRR5687225_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/002/SRR5687232/SRR5687232_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/007/SRR5687227/SRR5687227_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/004/SRR5687224/SRR5687224_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/006/SRR5687226/SRR5687226_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/005/SRR5687225/SRR5687225_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/002/SRR5687232/SRR5687232_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/000/SRR5687230/SRR5687230_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/001/SRR5687231/SRR5687231_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/004/SRR5687224/SRR5687224_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/008/SRR5687228/SRR5687228_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/009/SRR5687229/SRR5687229_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/000/SRR5687230/SRR5687230_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/001/SRR5687231/SRR5687231_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/007/SRR5687227/SRR5687227_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR568/008/SRR5687228/SRR5687228_2.fastq.gzprimaryOK200GenomicsODS, TFGB, NHGRI/NIHhttps://www.ebi.ac.uk/ena/browser/view/PRJNA390612Mus musculusxref:PubMed:28819283The recurrent chromosome 16 inversion in acute myeloid leukemia generates a fusion gene between CBFB and MYH11, which in turn encodes a chimeric protein CBFβ-SMMHC (core binding factor β-smooth muscle myosin heavy chain). We previously demonstrated that CBFβ-SMMHC needs its C terminal domains for leukemogenesis. In this study, we generated a new Cbfb-MYH11 knock-in mouse model to dissect the role of the multimerization domain at the C terminus of CBFβ-SMMHC. Specifically, we mutated six amino acids in the helices D and E (mDE) of the assembly competent domain, which is important for SMMHC multimerization. We found that the embryos with the mDE mutation (Cbfb+/mDE) did not develop hematopoietic defects seen in embryos with full-length CBFβ-SMMHC (Cbfb+/MYH11). More importantly leukemia development was abolished in the adult Cbfb+/mDE mice even after mutagenesis treatment. In addition, gene expression profile of the hematopoietic cells from the Cbfb+/mDE mice was more similar to that of Cbfb+/+ mice than the Cbfb+/MYH11 mice. Our data suggest that the C terminal multimerization domain is required for the defects in primitive and definitive hematopoiesis caused by CBFβ-SMMHC, and it is also essential for leukemogenesis caused by CBFβ-SMMHC. Overall design: RNA-seq of Bone marrow c-KIT+ cells from WT, Cbfb +/mDE, Cbfb +/MYH11 miceENAleukemia, Myosin heavy chain, Leucocythemia, single-organism developmental process, postnatal development, postnatal growth, Leucocythemias, Myosin heavy chain 11, growth and development, SM1, FAA4., SM2, SMMHC, smooth muscle isoform, Leukemias, AAT4, development, smMHC, leukaemia NOS, AV071570, SMHC, Leucocythaemia, leukaemia, growth, LeucocythaemiasMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisfalseMus musculusThe C-terminal multimerization domain is essential for leukemia development by CBFβ-SMMHC2025-09-242018-06-16PRJNA390612GSE1000611009028819283