Key Points• PD-L1 expression is associated with poor prognosis in DLBCL.• The double-staining technique is a useful method for identifying and distinguishing PD-L1 1 DLBCL.Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1 1 DLBCL. (P 5 .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1

Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.

Aberrant hypermethylation of tumor suppressor genes plays an important role in the development of many tumors. Recently identified new DNA methyltransferase (DNMT) genes, DNMT3A and DNMT3B, code for de novo methyltransferases. To determine the roles of DNMT3A, DNMT3B, as well as DNMT1, in the development of leukemia, competitive polymerase chain reaction (PCR) assays were performed and the expression levels of DNMTs were measured in normal hematopoiesis, 33 cases of acute myelogenous leukemia (AML), and 17 cases of chronic myelogenous leukemia (CML). All genes were constitutively expressed, although at different levels, in T lymphocytes, monocytes, neutrophils, and normal bone marrow cells. Interestingly, DNMT3B was expressed at high levels in CD34 ؉ bone marrow cells but down-regulated in differentiated cells. In AML, 5.3-, 4.4-, and 11.7-fold mean increases were seen in the levels of DNMT1, 3A, and 3B, respectively, compared with the control bone marrow cells. Although CML cells in the chronic phase did not show significant changes, cells in the acute phase showed 3.2-, 4.5-, and 3.4-fold mean increases in the levels of DNMT1, 3A, and 3B, respectively. Using methylation-specific PCR, it was observed that the p15 INAK4B IntroductionDNA methylation plays an important role in tissue-and stagespecific gene regulation, 1,2 genomic imprinting, 3,4 and X-chromosome inactivation, 5 and has been shown to be essential for normal mammalian development. 6 Recent studies have revealed that both global DNA hypomethylation and regional hypermethylation occur in tumorigenesis. [7][8][9] Such aberrant DNA methylation is observed in a nonrandom, tumor type-specific manner. 10 In particular, certain types of tumors show regional hypermethylation of CpG islands associated with the promoter regions of tumor suppressor genes, such as RB, 11 VHL, 12 p16 INAK4A , 13 and hMLH1. 14 Furthermore, the regional hypermethylation is often associated with the inactivation of the tumor suppressor genes. 15 These data suggest that this epigenetic process has a pathogenetic role in the clonal evolution of cancer. 9 In hematologic malignancies, aberrant DNA hypermethylation is thought to have relevance to leukemogenesis. 16 For example, during the progression of chronic myelogenous leukemia (CML), the ABL1 promoter of the BCR-ABL fusion gene becomes significantly hypermethylated. 17,18 Also, aberrant hypermethylation of the p15 INAK4B tumor suppressor gene is associated with its inactivation in at least half of the patients with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). 19,20 Furthermore, hypermethylation of p15 INAK4B is observed concomitant with the disease progression in myelodysplastic syndrome (MDS). 21 In addition to these tumor-related genes, a number of other genes are concurrently hypermethylated in AML, 22 suggesting that there might be a dysregulation in the normal DNA methylation mechanism, by which the leukemic cells become predisposed to hypermethylation.Until recently, only one mammalian DNA methyl...

We investigate the vortex lattice solution in a (2+1)-dimensional holographic model of superconductors constructed from a charged scalar condensate. The solution is obtained perturbatively near the second-order phase transition and is a holographic realization of the Abrikosov lattice. Below a critical value of magnetic field, the solution has a lower free energy than the normal state. Both the free energy density and the superconducting current are expressed by nonlocal functions, but they reduce to the expressions in the Ginzburg-Landau (GL) theory at long wavelength. As a result, a triangular lattice becomes the most favorable solution thermodynamically as in the GL theory of type II superconductors.Comment: v2: minor changes, references added; 11 pages, 2 figures: version to appear in PR

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