Sensitivity assays demonstrated that AMP-E can detect <i>MLL-AFF1</i> in MV4-11 cell dilutions of 10<sup>-7</sup> and transcripts down to 0.005 copies/ng.<b>Implications:</b> This study demonstrates a NGS methodology with improved sensitivity compared with current diagnostic methods for <i>MLL</i>-rearranged leukemia.
We provide evidence that oligomerization is the dominant mechanism driving oncogenesis from rare MLL translocation partners and employ our mechanistic understanding of MLL-AF6 to examine how dimers induce leukemia.
Heterozygous conditional inactivation of <i>Setd2</i> in a murine model decreased the latency of MLL-AF9-induced leukemia and caused resistance to cytarabine treatment in vivo, whereas homozygous loss delayed leukemia formation.
Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53).
A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL-AF9, MLL-AF4, and AML1-ETO.
Notably, inhibition of the core BER factor Apurinic-apyrimidinic endonuclease 1 protects against MLLbcr cleavage in tumour and human cord blood-derived haematopoietic stem/progenitor cells, harbouring the cells of origin of leukaemia.
Using an MLL-AF9 murine leukemia model and serial transplantation studies, we show that ZFP521 is not required for leukemogenesis, although its absence leads to a significant delay in leukemia onset.
In conclusion, our findings identify ZNF521 as a critical effector of MLL fusion proteins in blocking myeloid differentiation and highlight ZNF521 as a potential therapeutic target for this subtype of leukemia.
CD19 and CD20 antigen loss in acute lymphocytic leukemia and chronic lymphocytic leukemia, respectively, and lineage switching in leukemia associated with mixed lineage leukemia (MLL) gene rearrangements are well-documented evidences in this regard.
In this review, we will discuss the normal biological roles of MLL1 and its fusion partners, how these roles are hypothesized to be dysregulated in the context of <i>MLL1</i> rearrangements, and the clinical manifestations of this group of leukemias.