MYH11 (Myosin Heavy Chain 11)

By using the conventional and molecular cytogenetic technique, the cytogenetic anomalies found were 35 numerical chromosomal abnormalities, 10 (9;22)(q34;q11) [four ALL, one AML, five chronic myeloid leukemia (CML)] translocations, nine (15;17)(q24;q21) translocations, three (14;14)(q11;q32) translocations, two (4;11)(q21;q23) translocations, one (1;14)(p32;q11) translocation, one (7;14)(qter;q11) translocation, one (8;21)(q22;q22) translocation, one (9;14)(p12;q32) translocation, seven rearrangements of the MLL gene and two rearrangements of the core-binding factor subunit beta∕myosin heavy chain 11 (CBFB∕MYH11) gene. The use of conventional and molecular cytogenetic analysis is one of the most important prognostic indicators in acute leukemia patients, allowing the identification of biologically distinct subtypes of disease and selection of appropriate treatment approaches.

Our data, together with previously reported abnormal karyotypes in angioleiomyomas, show the presence of two recurrent genetic pathways in this tumor type: The first is characterized by presence of the translocation t(4;5)(p12;q32), which generates a CARMN::TXK chimera. The second is recurrent rearrangement of Xq22 resulting in overexpression of IRS4.

Using whole genome and Sanger sequencing, the breakpoints were identified as being located in intron 5 of CBFB and intron 7 of PPP1R7. A microhomology of CAG was found in the break and reconnection sites of CBFB and PPP1R7, thus supporting the formation of CBFB::PPP1R7 by microhomology-mediated end joining.

Our study provided a TEX-derived system that can be applied for the immune subtyping of cancers and may have implications for the further optimization of personalized cancer immunotherapy.

DNMT3B inhibits MYH11 expression by promoting its DNA methylation, thereby attenuating the repressive effect of MYH11 on the transcriptional of TNFRSF14 and promoting the progression of GC.

We demonstrate that RUNX1 directly interacts with DNMT3A and that CBFB-MYH11 fusion protein sequesters RUNX1 in the cytoplasm, thereby preventing RUNX1 from interacting with and recruiting DNMT3A to its target genes. Our results identify a novel regulation of DNA methylation and provide a molecular basis how CBFB-MYH11 fusion contributes to leukemogenesis.