MYC upregulation simultaneously sensitizes cells to apoptosis and activated lymphocytes and lymphoma cells have pro-survival attributes that allow MYC-driven proliferation to prevail.
MYC translocations occurred as single hit (only MYC rearranged, 63%) or multiple hit lymphoma (37%) and presented as acute leukemia (AL) (14%), Burkitt lymphoma (30%), chronic lymphocytic leukemia (CLL) (21%) or other mature B-cell neoplasms (35%).
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.
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.
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.
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.
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.
Furthermore, MYC possesses nontranscriptional functions other than transcriptional controls on genes regulating cell growth and may also influence the lymphoma microenvironment.
Furthermore, we show that the ESC program is correlated with transcriptional programs maintaining tumor phenotype in transgenic MYC-driven mouse models of lymphoma.
Here, we demonstrate that coordinated targeting of rDNA transcription and PI3K-AKT-mTORC1-dependent ribosome biogenesis and protein synthesis provides a remarkable improvement in survival in MYC-driven B lymphoma.
Here, we provide biological insight on the function of MYC-regulated miRNAs, the mechanisms of MYC-induced miRNA repression, and the complicated feedback circuitry underlying lymphoma progression, as well as potential therapeutic targets in aggressive B-cell lymphomas.
Here, we report that the Zn(2+)-finger transcription factor ASCIZ (ATMIN, ZNF822) synergizes with MYC to activate the expression of dynein light chain (DYNLL1, LC8) in the murine Eμ-Myc model of lymphoma.
However, APE1 is unexpectedly dispensable for SHM in the S region and translocation between immunoglobulin heavy chain (IgH) and c-myc genes in the mouse B lymphoma cell line, CH12F3-2A.