Chromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene occur in primary and treatment-related leukemias and confer a poor prognosis.
The established cell line, TZ-1, could provide a valuable model in the analysis of the pathogenesis of MLL-EPS15-positive leukemia and in the development of new agents for this type of leukemia.
EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human 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.
On the other hand, high MEL1 expression was detected in myelocytic-lineage (designated as e-M0/M1/M2 subtype) and e-M4/M5 subtype leukemia without MLL rearrangements, and its prognostic association was independent from the subtypes.
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.
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.
Recurrent chromosomal translocations involving the mixed lineage leukaemia (MLL) gene initiate aggressive forms of leukaemia, which are often refractory to conventional therapies.
MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias.
This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL-1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors.
Importantly, hypermethylation of DLX3 significantly reduces its expression in MLL-AF4 rearranged leukemias while methylation is almost absent in TEL-AML1 positive ALL specimens.
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.
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.
Leukemias with t(4;11)(MLL-AF4) were found to be resistant to the cell death that results from serum deprivation in vitro when compared with B lineage acute leukemias without t(4;11)(MLL-AF4).
The role of Cdc42 in hematopoietic cell transformation and leukemia progression has been studied in an acute myeloid leukemia model using the MLL-AF9 oncogene-induced transformation and a Cdc42 conditional gene-targeted mouse model.
Inactivation of MLL1 leads to decreased expression of genes bound by NHA9 and MLL1 and reverses a gene expression signature found in NUP98-rearranged human leukemias.
Using an MLL-AF9-induced murine leukemia model, we demonstrated that the deletion of ChREBP resulted in the blockage of the differentiation of LICs and significantly reduced survival in ChREBP-null leukemic mice.