affecting the activities of relipidated or cell surface TF, exactly as observed. To test this hypothesis we have examined bovine PDI for traces of PL. The activation of prothrombin by factor Xa/Va is highly sensitive to the presence of PL. As noted with sTF, addition of bovine PDI, but not rhPDI, markedly increased prothrombin activation ( Figure 1B). Addition of annexin V, a phospholipid binding protein, completely attenuated the bovine PDI-mediated increase in sTF activity ( Figure 1C) and prothrombin activation (data not shown), further strengthening our hypothesis that the observed enhancing effects of bovine PDI stem from contamination of the reagent with PL. Consistent with this notion is our observation that pretreatment of bovine PDI with phospholipase C, which inhibits PL function by cleaving it at the phosphate group, abolished the enhancing effect of bovine PDI on sTF. Finally, in contrast to the data obtained with immunoprecipitation studies, 5 we found no evidence for the direct interaction of PDI with TF in Biacore binding studies ( Figure 1E). In summary, the enhancing effect of bovine PDI is not limited to its effects on sTF but also extends to activation of prothrombin by factors Xa/Va. Our present data suggest that the effect of bovine PDI on sTF (and prothrombin activation) is probably an artifact due to contamination of commercial bovine PDI with traces of PL. To the editor: Aberrant Ikaros, Aiolos, and Helios expression in Hodgkin and non-Hodgkin lymphomaIkaros transcription factors are regulators of lymphocyte development, and changes in their expression result in lymphoma development in mice. 1 Although expression of Ikaros family members has been studied in different leukemias, 2-4 it has not been previously reported in lymphoma. Thus, we tackle the question whether there is a quantitative difference in distribution of Ikaros, Aiolos, and Helios mRNA between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Formalin-fixed and paraffinembedded sections of lymph nodes from 41 patients were analyzed. 5 NHL is represented by the most frequent indolent follicular center cell lymphoma (FCC), the aggressive diffuse large B-cell lymphoma (DLBCL) and a less frequent anaplastic large cell lymphoma (ALCL; Figure 1). Subclassification of HL (mixed cellularity or nodular) did not reveal any difference in Ikaros family expression, so we rather present them as a single group. The experiments were approved by the Ethics Committee of the University of Zugreb Medical School. Informed consent was obtained in accordance with the Declaration of Helsinki. Figure 1 shows that the relative quantity of Ikaros and Helios mRNA is not statistically different among HL, DLBCL, FCC, ALCL, and normal controls tested (Ikaros: F (4,42) ϭ 0.612, P ϭ .656; Helios: F (4,42) ϭ 0.858, P ϭ .497; one-way ANOVA) On the other hand, analysis of the third Ikaros family member, Aiolos, showed a statistically significant difference among groups (F (4,42) ϭ 7.052, P Ͻ .01, one-way ANOVA) due to increase of its expression in FCC-NHL...

B cell lymphomas mainly arise from different developmental stages of B cells in germinal centers of secondary lymphoid tissue. There are a number of signaling pathways that affect the initiation and development of B cell lymphomagenesis. The functions of several key proteins that represent branching points of signaling networks are changed because of their aberrant expression, degradation, and/or accumulation, and those events determine the fate of the affected B cells. One of the most influential transcription factors, commonly associated with unfavorable prognosis for patients with B cell lymphoma, is nuclear phosphoprotein MYC. During B cell lymphomagenesis, oncogenic MYC variant is deregulated through various mechanisms, such as gene translocation, gene amplification, and epigenetic deregulation of its expression. Owing to alterations of downstream signaling cascades, MYC-overexpressing neoplastic B cells proliferate rapidly, avoid apoptosis, and become unresponsive to most conventional treatments. This review will summarize the roles of MYC in B cell development and oncogenesis, as well as its significance for current B cell lymphoma classification. We compared communication networks within transformed B cells in different lymphomas affected by overexpressed MYC and conducted a meta-analysis concerning the association of MYC with tumor prognosis in different patient populations.

Satellite DNAs are tandemly repeated sequences preferentially assembled into large arrays within constitutive heterochromatin and their transcription is often activated by stress conditions, particularly by heat stress. Bioinformatic analyses of sequenced genomes however reveal single repeats or short arrays of satellite DNAs dispersed in the vicinity of genes within euchromatin. Here, we analyze transcription of a major human alpha satellite DNA upon heat stress and follow the dynamics of “silent” H3K9me3 and “active” H3K4me2/3 histone marks at dispersed euchromatic and tandemly arranged heterochromatic alpha repeats. The results show H3K9me3 enrichment at alpha repeats upon heat stress, which correlates with the dynamics of alpha satellite DNA transcription activation, while no change in H3K4me2/3 level is detected. Spreading of H3K9me3 up to 1–2 kb from the insertion sites of the euchromatic alpha repeats is detected, revealing the alpha repeats as modulators of local chromatin structure. In addition, expression of genes containing alpha repeats within introns as well as of genes closest to the intergenic alpha repeats is downregulated upon heat stress. Further studies are necessary to reveal the possible contribution of H3K9me3 enriched alpha repeats, in particular those located within introns, to the silencing of their associated genes.

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

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