Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene.
From 5% to 20% of patients with agnogenic myeloid metaplasia (AMM) will evolve into a terminal leukemic phase; N-RAS gene mutations are the most common gene abnormalities detected in patients with leukemia.
Since no NRAS mutations were detected among the t(8;21) samples and only 1 was found in the inv(16) group, we conclude that acute myeloid leukaemias with t(8;21) or inv(16) generally arise and progress without the involvement of NRAS mutations.
These findings indicate that the N-ras mutations may not always be characterized simply by an accumulative process and that the activated N-ras gene alone is not sufficient to cause leukemia.
Because the INS gene, which was also translocated, is probably located proximal to HRAS1 on chromosome 11p, it is unlikely that HRAS1 was near the chromosome 11 breakpoint or involved in this leukaemia.
These observations suggest that the chromosomal abnormality may precede activation of the N-ras gene in these patients, and that both the chromosomal abnormality and the activated N-ras oncogene contribute to the development of leukemia.
Our observation of the mutation at codon 13 in leukaemic cell DNAs from all three cases suggests that activation of the N-ras gene is important in the development of leukaemia in some MDS cases.
Characterization of a patient with concurrent BRAF-mutant melanoma and NRAS-mutant leukemia treated intermittently with combined BRAF and MEK inhibition provides new insights into the potential clinical and molecular effects of this therapeutic strategy.
The BRAF kinase is mutated, typically Val 600→Glu (V600E), to induce an active oncogenic state in a large fraction of melanomas, thyroid cancers, hairy cell leukaemias and, to a smaller extent, a wide spectrum of other cancers.
The ERK1/2 (extracellular signal-regulated kinase 1 and 2) pathway, comprising the protein kinases RAF (v-raf-1 murine leukemia viral oncogene homolog 1), MEK1/2 (mitogen-activated protein kinase or ERK kinase 1 and 2) and ERK1/2 is frequently de-regulated in human cancers, due to mutations in RAS or BRAF (v-raf-1 murine leukemia viral oncogene homolog B1).
None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAFV600E variant, including 38 patients with splenic marginal-zone lymphomas or unclassifiable splenic lymphomas or leukemias.
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.
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.
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.