New developments in the pathology of malignant lymphoma: a review of the literature published from August to December 2008

Abstract

Biology of lymphomaThe pathogenesis of malignant lymphomas remains poorlyunderstood. Several approaches to detect the genesinvolved are available. Bric et al. [1] focus on the detectionof tumor suppressor genes by using RNA interference ofspecific gene products in a known mouse model forlymphoma development. They detected more than 10 newcandidate tumor suppressor genes, showing the validity oftheir functional approach. In a similar approach in adifferent mouse model, Meacham et al. [2] found manynew gene alterations in a mouse lymphoma, several ofwhich involved genes associated with cell motility. Theywere also able to show that these genes were bona fide drugtargets.Gloghini et al. [3] studied 14 cell lines and 89 lymphomatissues for expression of histone deacetylases (HDAC). Incell lines, low expression HDAC6 was associated withgrowth inhibitory effects of HDAC inhibitors, but it israrely expressed in tissue samples of diffuse large B celllymphoma (DLBL) and Hodgkin lymphoma (HL).B cell lymphomasA crucial element in cancer cells is the unlimited potentialto replicate; thus, cancer cells need telomerase activity forsynthesizing telomeric DNA. Most differentiated cells lackthis activity, but in cancer cells, there is low-levelexpression due to altered methylation status of the gene.In B lymphocytes, the situation is different since they havetelomerase activity and normal methylation status. Bougelet al. [4] show that by downregulating Pax5, this activitydisappears, indicating the importance of that gene for thepotential of normal B cells to undergo many cell divisions.The TCL-1 gene is often deregulated in B cell lymphomasdue to hypermethylation of several genes. Balatoni et al. [5]show that one of these Stk39-encoded proteins (SPAK),which regulates stress response, is downregulated in B celllymphomas resulting in apoptosis resistance.Chromosomal breaks are dangerous to cells; nevertheless,they occur often in germinal center B cells. Zhou et al. [6]found in a mouse model that MDM2, which inducesapoptosis in cells with chromosomal breaks, is downregu-lated in germinal center B cells due to lack of expression ofIFNregulatoryfactor8andthustoleratingchromosomalbreaks needed for B cell antigen receptor rearrangement.It is still unclear why the Epstein–Barr virus (EBV) canresultinsomanydifferentdiseases.Lorenzettietal.[7]linkedgenomic variation of the BZLF1 gene of the virus to 13cases of lymphoma and 10 of infectious mononucleosis inchildren. They were able to find significance but no absolutedifference indicating that other genes or factors are importanttoo.Follicular lymphoma (FL) can have various amounts ofdiffuse growth areas. Higashi et al. [8] show that theexpression of CD44 and variants is associated with diffuseareas.In primary mediastinal large B cell lymphoma and HL,inactivating mutations in SOCS1, an inhibitor of Januskinase/signal transducers and activators of transcription(JAK/STAT) signaling, contributes to deregulated STATactivity. Mottok et al. [9] show that these mutations, whichare preferentially targeted to somatic hypermutation hotspotmotifs and frequently inactivating, occur at low level in