Aberrant Ikaros, Aiolos, and Helios expression in Hodgkin and non-Hodgkin lymphoma

Abstract

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...

Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing

“…The IKZF3 gene (Aiolos) encodes for a member of the Ikaros family of zinc-finger proteins that is important in the regulation of B-lymphocyte proliferation and differentiation and is overexpressed in various lymphomas (Antica et al, 2008;Cortes and Georgopoulos, 2004). IKZF3 mutations have been reported in chronic lymphocytic leukemia (Landau et al, 2015).…”

Aiolos Promotes Anchorage Independence by Silencing p66Shc Transcription in Cancer Cells

“…Aiolos is highly expressed and may promote survival in B-cell leukemia and certain lymphomas; conversely, Aiolos is absent in acute lymphoblastic leukemia (Antica et al, 2008; Billot et al, 2011; Duhamel et al, 2008; Holmfeldt et al, 2013; Niebuhr et al, 2013; Romero et al, 1999). Further, Aiolos has been detected in multiple malignant solid tumor cell lines including MCF-7, SW480, HEK, PC3 and HeLa (Billot et al, 2010).…”

Overexpression of AIOLOS inhibits cell proliferation and suppresses apoptosis in Nalm-6 cells

“…In addition, AIOLOS null mutation in mice causes B-cell hyperproliferation, elevated serum antibody levels, auto-antibody formation and development of lymphomas demonstrating tumor suppressor function (10). Deregulated AIOLOS expression has been associated with adult B-cell ALL and chronic lymphocytic leukemia (CLL) in human patients (11)(12)(13) and aberrant AIOLOS expression levels have been reported in lymphoma (14). However, the function of AIOLOS in childhood BCP-ALL is not fully understood.…”