There were 47 DTHLs, 36 cases with MYC and BCL2 and/or BCL6 extra signals (ES) and/or rearrangements (ES group, excludes DTHLs), 9 with MYC rearrangements only (single-hit lymphoma), and 95 with no MYC abnormalities (NM).
Inhibition of BET bromodomain-promoter interactions and subsequent reduction of MYC transcript and protein levels resulted in G(1) arrest and extensive apoptosis in a variety of leukemia and lymphoma cell lines.
Most of the refractory patients exhibit double-hit lymphoma (MYC-BCL2 rearrangement) or double-protein-expression lymphoma (MYC-BCL2 hyperexpression) which have a more aggressive clinical picture.
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.
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.
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.
Finally, picolog was highly potent at 100 micrograms/kg and well tolerated at doses ranging from 100 micrograms/kg to 1 milligram/kg in vivo for the treatment of our aggressive model of MYC-induced lymphoma.
Patients with abdominal nodal disease had inferior lymphoma specific survival (p=0.04) and presented with higher age adjusted IPI (p<0.001), lactate dehydrogenase (p<0.001) and more often advanced stage (p<0.001), bulky disease (p<0.001), B-symptoms (p<0.001), and double expression of MYC and BCL2 (p=0.02) compared to patients without nodal abdominal involvement, but less often extranodal involvement (p<0.02).
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.
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.
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.
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.