These preliminary data suggest that flt3-ITD mutations may play an important role in leukemogenesis in a proportion of children, particularly in the case of AML.
We conclude that concentrations of E2 and 4-OH-E2 that may occur during pregnancy, or during use of oral contraceptives, can cause aberrations of the MLL gene and could thus be a factor in the early events of leukemogenesis occurring in utero.
We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11 D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo.
These data infer that IGF2BP1 is a potent regulator of ETV6/RUNX1 mRNA stability and potentially link this evolutionary-highly conserved protein to cell transformation events in ETV6/RUNX1-mediated leukemogenesis of t(12;21)(p13;q22)-positive ALL.
Our results strongly suggest that acquisition of a CSF3R mutation is an early event in leukemogenesis that has to be accompanied by cooperating molecular events, which remain to be defined.
It has been demonstrated that the chromosomal translocation t(7;11)(p15;p15) in patients with human acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) invariably involves fusion of the nucleoporin gene, NUP98, on chromosome 11 and the class 1 HOX gene, HOXA9, on chromosome 7, and that the fusion gene NUP98-HOXA9 is an important gene in myeloid leukemogenesis.
To evaluate whether both AML1 and FLT3 mutations contribute to leukemogenesis, we analyzed mutations of these genes in AML M0 subtype in whom AML1 mutations were predominantly observed.
Presence of t(8;14)(q24;q32) and the c-myc gene rearrangement after transformation suggested that the chromosomal translocation followed by the activation of the c-myc proto-oncogene might be involved in the Burkitt's type transformation of the FAB-L2 leukemic clone, but not in the leukemogenesis of the initial FAB-L2 leukemia.
Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level.
Our results provide direct evidence that AML1-ETO is critical for causing myeloid leukemia, but one or more additional mutations are required for leukemogenesis.
Active mutations of Notch1 play pivotal roles during leukemogenesis, but the downstream targets and molecular mechanisms of activated Notch1 signaling have not yet been fully clarified.
Here, we investigated the cooperation of mutant DNMT3A and NRAS in leukemogenesis by generating a double knock-in (DKI) mouse model harboring both Dnmt3aR878H and Nras G12D mutations.
Since the TCL6 gene was expressed in T-cell leukemia carrying a t(14;14)(q11;q32.1) chromosome translocation and was not expressed in normal T-cells (just like the TML1 and TCL1 genes), it is also a candidate gene potentially involved in leukemogenesis.Oncogene (2000).
She provides an overview of leukemias that are common in pediatric malignancies but rarely observed in adults, including the TEL-AML1 (ETV6-RUNX1) fusion associated with pediatric B-cell ALL, the OTT-MAL fusion associated with infant megakaryoblastic leukemia, PTPN11 mutations in juvenile myelomonocytic leukemia, and MLL fusion genes in leukemogenesis, among others.
In conclusion, cooperation between aberrant expression of RasGRP1, a strong activator of Ras, and secondary gain-of-function mutations of NOTCH1 have an important role in T-cell leukemogenesis.
Taken together, Flt3-ITD mutations induce factor-independent growth and leukemogenesis of 32D cells that are mediated by the Ras and STAT5 pathways.(Blood.2000;96:3907-3914)
Translocations and somatic mutations are common genetic alterations of the BCL-6 gene on chromosome 3q27 in B-cell lymphoma, with implications for lymphomagenesis.
This R107L mutation remained in leukocytes of the remission stage in which GATA1 mutation disappeared, suggesting the TRIB1 mutation is an earlier genetic event in leukemogenesis.