KMT2A-MLLT10 is one of the common chimeric genes diagnosed in acute leukemia with KMT2A rearrangement (8%), especially in acute myeloid leukemia (AML; 18%).
Although it is presently unclear whether these sarcomas belong to a single group, the well-established role of KMT2A fusions as drivers of acute leukaemia and a recent publication regarding identification of YAP1-KMT2A in one unclassifiable sarcoma support the significance of these fusions.
Overlap of MLL bcr sequences associated with both infant acute leukemia and therapy-related leukemia following exposure to the topoisomerase II inhibitor etoposide led to the hypothesis that exposure during pregnancy to biochemically similar compounds may promote infant acute leukemia.
This study aimed at assessing if the cell-of-origin of t(4;11) MLL-AF4 acute leukemia is sensitive to a viral or bacterial mimic and if maternal immune activation can lead to a full-blown leukemia.
Chromosomal rearrangements involving the mixed-lineage leukemia (MLL1) gene are common in a unique group of acute leukemias, with more than 100 fusion partners in this malignancy alone.
Acute leukemias (AL) with a Mixed Lineage Leukemia (MLL) gene rearrangement (MLLr) represent a group of leukemic entities conferring intermediate to adverse prognoses.
This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.
Furthermore, compounds 1, 23 and 44 were chosen to evaluate for their antiproliferative activities on the MLL-AF4-expression acute leukemia cell line (MV4-11), other cancer cell lines (MDA-MB-231, A549, 22Rv1) and the non-cancer cell lines (HUV-EC-C, MRC5, RPTEC).
The breakpoint cluster region of the MLL gene (MLLbcr) is frequently rearranged in therapy-related and infant acute leukaemia, but the destabilizing mechanism is poorly understood.
We demonstrate that one of the ENL YEATS-selective inhibitors, XL-13m, engages with endogenous ENL, perturbs the recruitment of ENL onto chromatin, and synergizes the BET and DOT1L inhibition-induced downregulation of oncogenes in MLL-rearranged acute leukemia.
The protein-protein interaction between menin and mixed-lineage leukemia 1 (MLL1) plays an important role in development of acute leukemia with translocations of the MLL1 gene and in solid tumors.
By contrast, MLL-translocations in acute leukemia patients are hard to treat, display a high relapse rate and the overall survival rate is still very poor.
Chromosomal rearrangements of the mixed lineage leukemia (MLL/KMT2A) gene leading to oncogenic MLL-fusion proteins occur in ~10% of acute leukemias and are associated with poor clinical outcomes, emphasizing the need for new treatment modalities.
The mixed-lineage leukemia 1 (MLL1) gene (now renamed <i>Lysine [K]-specific MethylTransferase 2A</i> or <i>KMT2A</i>) on chromosome 11q23 is disrupted in a unique group of acute leukemias.
Here, using unbiased CRISPR-Cas9 technology to perform a genome-scale loss-of-function screen in an MLL-AF4-positive acute leukaemia cell line, we identify ENL as an unrecognized gene that is specifically required for proliferation in vitro and in vivo.
Mutations in <i>SETD2</i><i>,</i> encoding the histone 3 lysine 36 trimethyltransferase, are enriched in relapsed acute lymphoblastic leukemia and MLL-rearranged acute leukemia.
The hallmark of the AOP is the formation of MLL gene rearrangements via topo II poisoning, leading to fusion genes and ultimately acute leukaemia by global (epi)genetic dysregulation.