In all four BL lines studied (JD38, AG876, KK124, and Daudi), there was persistent or increased expression of both c-mu and c-myc genes (detected with a third exon c-myc probe), in contrast to the decreased expression of the c-myc gene observed in the three Epstein-Barr virus transformed lines studied (A3317, TC84, and CB34).
Mature B-cell acute lymphoblastic leukemia (ALL) is typically associated with the FAB-L3 morphology and rearrangement of the MYC gene, features characteristic of the leukemic phase of Burkitt's lymphoma.
In the Burkitt's lymphoma (BL) cell line BL67 the first exon of the c-myc gene is fused to the mu-switch region of the immunoglobulin heavy-chain gene (IgH).
In Burkitt's lymphoma (BL) cells characteristic chromosomal translocations juxtapose the MYC oncogene to one of the three immunoglobulin (IG) gene loci.
Here, we report sAJM589, a novel small molecule Myc inhibitor, identified from a PCA-based high-throughput screen. sAJM589 potently disrupts the Myc-Max heterodimer in a dose dependent manner with an IC<sub>50</sub> of 1.8 ± 0.03 μM. sAJM589 preferentially inhibits transcription of Myc target genes in a Burkitt lymphoma cell model, P493-6.
Patients demonstrating a terminal deoxynucleotidyl transferase (TdT)-positive precursor B cell phenotype with IGH-MYC rearrangement have been reported to be molecularly distinct from BL and closer to B-ALL/LBL.
One miRNA, hsa-miR-1204, resides within a previously described PVT1 exon (1b) that is often fused to the immunoglobulin light chain constant region in vBLs and is present in high copy number in MYC/PVT1-amplified tumors.
We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines.
Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples.
Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.
Indeed, the lack of CD5 and expression of CD10 associated with MYC rearrangement detected on interphasic nuclei could support the diagnosis of diffuse large B-cell lymphoma or Burkitt lymphoma.
Chromosome 8q24/MYC rearrangement is associated with Burkitt lymphoma and some aggressive B-cell lymphomas, but is rare in chronic lymphocytic leukemia.
MYC protein staining of >50% of lesional cells was identified in 60% of Burkitt lymphomas, 50% of B lymphoblastic lymphomas, 33% of T lymphoblastic lymphomas, 31% of rhabdomyosarcomas, 33% of Ewing sarcomas, and 25% of soft tissue sarcomas, not otherwise specified.
The translocated c-myc gene in AW-Ramos, a Burkitt lymphoma cell line carrying the 8;14 translocation, is expressed at 2- to 5-fold higher levels than c-myc in lymphoblastoid cell lines.
Whereas TFE3 is typically fused to partner proteins in subsets of renal tumors, we found that wild-type, unfused TFE3 stimulates clonogenic growth in a cell-based assay, suggesting that dysregulated expression, rather than altered function of TFEB or TFE3 fusions, may confer neoplastic properties, a mechanism reminiscent of MYC activation by promoter substitution in Burkitt's lymphoma.