From these studies it is inferred that secondary dysregulation of a c-MYC in a lymphoma tumor carrying dysregulated BCL2 gene leads to rapid progression to high grade disease.
Similar to endemic and sporadic Burkitt's lymphoma, monoclonal B-lymphoma subsets were found to be infected with Epstein-Barr virus (EBV) or have c-myc gene rearrangements, suggesting a role for EBV infection or chromosomal translocation in a subset of AIDS NHLs.
Although with the majority of the specimens there was no obvious correlation between the morphologic cell type of lymphoma/leukemia and the c-onc RNA levels, interestingly two of the three samples diagnosed as chronic lymphocytic leukemia, B-cell type, showed considerably increased transcription of the c-myc gene relative to the other B-cell neoplasms.
We observed that in vivo phosphorylation of Thr-58 was absent in a lymphoma cell line with a mutant MYC allele containing a missense mutation flanking codon 58.
These results suggest that decreased expression of C-MYC and BCL2 may play a role in the molecular events that initiate and are responsible for the growth inhibition of Raji lymphoma xenografts by MP.
Mutation of Thr58 in lymphoma thus escapes this regulation resulting in accumulation of c-Myc protein, likely as part of the tumor progression.(Blood.2000;95:2104-2110)
Molecular cytogenetic investigation is essential to identify cases of high-grade leukaemia/lymphoma with concurrent translocations affecting the BCL2 and MYC loci.
A 53-year-old man diagnosed with chronic lymphocytic leukemia (CLL)-small lymphoma following splenectomy was found to have a t(8;14) with an apparent cryptic deletion of the MYC gene.
This finding supplies additional evidence that a translocation-mediated MYC activation may be an important event in the pathogenesis of this unique lymphoma.
To examine how the MYC and K-ras(G12D) oncogenes cooperate for the initiation and maintenance of tumorigenesis, we generated double conditional transgenic tumor models of lung adenocarcinoma and lymphoma.
To validate the role of gene signatures associated with MYC in human tumorigenesis, we examined the expression of human homologs in 273 published human lymphoma microarray datasets in Affymetrix U133A format.
To further analyze the impact of MYC-regulated miRNAs, we investigated a murine lymphoma model harboring the MYC transgene in a Tet-off system to control its expression.
We suggest that, concordant with the WHO classification to be published in 2008, the diagnosis of BL should be restricted to cases with expression of CD10 and BCL6, absence or very weak expression of BCL2 protein, a homogeneously very high proliferation index and a proven IG-MYC translocation without evidence of a chromosomal translocation typical for other lymphoma entities.
The importance of miRNAs in MYC-driven tumorigenesis has been enlightened by studying cell line and murine lymphoma models with conditional expression of MYC.
We report a unique KSHV(-) EBV(-) post-transplant effusion lymphoma associated with serum paraproteins, occurring in an HIV(-) individual, which had cytologic features and phenotype similar to PEL, and displayed a complex karyotype including isochromosome 12p and translocation t(8;22), resulting in rearrangement of c-MYC.
Our method can quantify amounts of MYC oncoprotein and B cell lymphoma protein-2 (BCL2) in Burkitt's and follicular lymphoma; identify changes in activation of extracellular signal-related kinases-1 (ERK1) and ERK2, mitogen-activated kinase-1 (MEK), signal transducer and activator of transcription protein-3 (STAT3) and STAT5, c-Jun N-terminal kinase (JNK) and caspase-3 in imatinib-treated chronic myelogeneous leukemia (CML) cells; measure an unanticipated change in the phosphorylation of an ERK2 isomer in individuals with CML who responded to imatinib; and detect a decrease in STAT3 and STAT5 phosphorylation in individuals with lymphoma who were treated with atorvastatin.
Dual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC.
Furthermore, we show that the ESC program is correlated with transcriptional programs maintaining tumor phenotype in transgenic MYC-driven mouse models of lymphoma.
Furthermore, MYC possesses nontranscriptional functions other than transcriptional controls on genes regulating cell growth and may also influence the lymphoma microenvironment.
This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements.