Our data suggest that aerobic glycolysis, or the Warburg effect, in BL cells is regulated by MYC expressed at high levels, whereas in LCLs, HIF1A is responsible for this phenomenon.
In conclusion, the miRs expression in B-NHLs[11q] provides a new suggestion, in addition to pathomorphological and clinical similarities between classical, i.e., MYC translocation-positive BL, and B-NHLs[11q], to recognize the B-NHLs[11q] subgroup of DLBCL/BL category as a MYC translocation-negative variant of BL in most cases, and points to the potential utility of miR-155/BIC/miR-21/miR-26a for the differential diagnosis of a heterogeneous category of DLBCL/BL.
We studied the microRNA profile of MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases in order to uncover possible differences at the molecular level.
We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL.
Burkitt lymphoma is a germinal center B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago.
MYC gene alterations in diffuse large B-cell lymphomas and in B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma are frequently associated with BCL2 or/and BCL6 translocations conferring a very aggressive behavior.
The BL cells showed a ∼90% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen in several non-BL cells.
Using flow cytometry we analyzed the expression of CD10, CD19, CD20, CD38 and CD45 in 53 patients with three distinct neoplasms with MYC rearrangements: Burkitt lymphoma (n = 12), double hit lymphoma (n = 17) and diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (n = 8).
Burkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is almost uniformly associated with translocations involving the gene for MYC on chromosome 8.
Although neither EBV nor MYC are sufficient to cause BL there is increasing information from techniques such as complete RNA sequencing that identify essential pathways that are activated in the pathogenesis of BL.
In human B-cell tumors, MYC rearrangements involving the 8q24 region and immunoglobulin heavy or light genes are a hallmark of Burkitt lymphoma (BL), but can also occur in other lymphoid malignancies, that include diffuse large B-cell lymphoma (DLBCL), B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU), plasma cell myeloma (PCM), mantle cell lymphoma (MCL) and plasmablastic lymphoma.
MYC IHC and FISH analyses were performed on 30 cases of diffuse large B cell lymphoma (DLBCL) with 80% or more Ki-67 index, one case of DLBCL transformed from follicular lymphoma, three cases of B cell lymphoma intermediate between DLBCL and Burkitt lymphoma (IM), six cases of Burkitt lymphoma (BL) and one case of reactive lymph node.
We observed an extent of IGH/MYC heterogeneity not previously reported in Burkitt lymphoma, including the novel finding of three fusion signals in two cases.
Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL).
The chromosomal translocation t(8;14)(q24;q32) with juxtaposition of MYC to enhancer elements in the immunoglobulin heavy chain (IGH) gene locus is the genetic hallmark of the majority of Burkitt lymphoma and a subset of Diffuse large B-cell lymphoma patients.
Most cases of MYC/BCL2 DHL morphologically resemble diffuse large B-cell lymphoma (DLBCL) or B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma.
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.
We identified ID3 mutations in lymphomas with chromosomal aberrations at cMYC and either BCL2 or BCL6 at a frequency intermediate between that of DLBCL and Burkitt lymphoma, hinting at a common pathway in lymphomagenesis for a subset of patients with DHL.