Patient-derived xenograft (PDX) models derived from patients with either MLL-r acute myeloid leukemia or MLL-r acute lymphoblastic leukemia (ALL) showed dramatic reductions of leukemia burden when treated with VTP50469.
Therefore, a new acute monocytic leukemia cell line with clear biological and molecular features was established and may be used in the research and development of new agents targeting KMT2A-associated leukemia.
Here, we studied the distribution and characteristics of Tregs in the LHME, investigated the effects of Treg ablation on leukemia progression, explored the mechanisms leading to Treg accumulation, and studied whether blocking Treg migration to the LHME delayed leukemia progression in MLL-AF9-induced mouse acute myeloid leukemia (AML) models using wildtype (WT) and Foxp3<sup>DTR/GFP</sup> mice.
Our findings demonstrate that the abnormal elevated expression of circAF4 regulates the cell growth via the circAF4/miR-128-3p/MLL-AF4 axis, which could contribute to leukemogenesis, suggesting that circAF4 may be a novel therapeutic target of MLL-AF4 leukemia.
The MLL1-AF10 fusion causes leukemia through recruiting the H3K79 histone methyltransferase DOT1L via AF10's octapeptide and leucine zipper (OM-LZ) motifs.
From our data we conclude that the scaffold protein 14-3-3θ enhances the aberrant activity of the chimeric transcription factor MLL-AF4 and, therefore, represents a new player in the molecular pathogenesis of t(4;11)-positive leukemia and a new promising therapeutic target.
In summary, our findings demonstrate that MN1 plays an essential role in MLL fusion leukemias and serve as a therapeutic target in MLL-rearranged acute myeloid leukemia.
There is a high unmet need to identify safer and more potent therapies for MLL-rearranged (MLL-r) leukemia that can be combined with established chemotherapeutics to decrease treatment-related toxicities.
In this review, we will discuss the role of MLL and its fusion partners in normal HSPCs and hematopoiesis, including the links between chromatin effectors, epigenetic landscapes, and leukemia development, and summarize current approaches to therapeutic targeting of <i>MLL</i>-r leukemias.
The protein-protein interaction (PPI) between WDR5 and MLL1 plays an important role in abnormal gene expression during tumorigenesis, disturbing MLL1-WDR5 interaction may have a potential for the treatment of leukemia harboring MLL1 fusion proteins.
We found that SOCS5 was differentially expressed in primary T-ALL and its expression levels were lowered in HOXA-deregulated leukemia harboring KMT2A gene rearrangements.
Moreover, development of additional methods to detect specific translocation partners of KMT2A and leukemia-specific targeting drugs is important to improve further the outcomes of KMT2A-rearranged AML.
Furthermore, auranofin delayed the progression of leukemia in MLL-rearranged patient-derived xenograft model and prolonged the survival of leukemic NSG mice.
Most importantly, IDA/MPEG-PLGA NPs significantly decreased the infiltration of leukemia blasts and improved the overall survival of MLL-AF9-induced murine leukemia compared with free IDA.
Dysregulation of MLL1 catalytic function is relevant to mixed-lineage leukemia, and targeting WDR5-MLL1 interaction could be a promising therapeutic strategy for leukemia harboring MLL1 fusion proteins.