NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib.

A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood. However, biomarkers to predict lymphocytosis or successful TFR are not well characterized. In order to clarify individual differences in NK cell responses among patients treated with Das, we retrospectively analyzed the association between polymorphisms in the natural killer group 2D receptor [NKG2D; also known as killer cell lectin like receptor K1 (KLRK1)] gene and clinical outcomes in 31 patients treated with Das as first-line treatment for CML. Patients with the NKG2D HNK1/HNK1 (high-cytotoxic activity-related allele on NKG2D hb-1) haplotype achieved MR4.5 more quickly than those with other haplotypes [hazard ratio (HR) 4.39; 95% confidence interval (CI) 2.75-118.6; P = 0.004]. In addition, NK cells with the NKG2D HNK1 allele exhibited enhanced phosphorylation of vav guanine nucleotide exchange factor 1 (VAV1) at Tyr174. These data suggest that NKG2D gene polymorphisms may represent candidate biomarkers for the prediction of TFR following Das treatment.

Clinical outcome of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma. The incidence of Epstein-Barr virus (EBV)-positive DLBCL in Asian and Latin American countries ranges from 8 to 10%. The prognosis of patients with EBV-positive DLBCL is controversial. To compare the clinical outcome of EBV-positive and EBV-negative patients with DLBCL in the rituximab era, we analyzed 239 patients with de novo DLBCL diagnosed between January 2007 and December 2011. The presence of EBV in lymphoma cells was detected using EBV-encoded RNA in situ hybridization, and it was found that 18 (6.9%) of 260 patients with diagnosed DLBCL tested positive. Among the 260 cases, 216 cases were treated with rituximab plus chemotherapy, as were 8 EBV-positive DLBCL patients. The median overall survival and progression-free survival times in patients with EBV-positive DLBCL were 8.7 months and 6.8 months, respectively. The median overall survival and progression-free survival could not be determined in EBV-negative DLBCL patients (P = 0.0002, P < 0.0001, respectively). The outcome of patients with EBV-positive DLBCL remains poor, even in the rituximab era.

Clinical and pathological features of B-cell non-Hodgkin lymphomas lacking the surface expression of immunoglobulin light chains.

BACKGROUND: The flow cytometric analysis of surface immunoglobulin light chains (sIgL) is used as a simple method for evaluating monoclonal B-cell proliferation. However, the sIgL expression, κ or λ, is occasionally undetectable in cases with B-cell non-Hodgkin lymphomas (B-NHL). The purpose of this study was to investigate the clinical and pathological characteristics of these B-NHL cases. METHODS: We retrospectively analyzed 50 cases with previously untreated sIgL-negative B-NHL. All of these cases had been diagnosed at Tokai University Hospital between January 2001 and February 2011. Their medical charts were reviewed. RESULTS: These cases had several clinical features: diffuse large B-cell lymphoma (DLBCL) (72%), a high serum lactate dehydrogenase level (66%), clinical stage III and IV (68%), and complex karyotypes (58%). Seven out of eight evaluated patients (87%) did not express cytoplasmic IgL, and the DNA rearrangement pattern of IgL showed diversity in 10 analyzed patients. The 5-year event-free survival of all the sIgL-negative B-NHL cases was significantly better with rituximab-containing chemotherapies in comparison to the regimens without it (57.9% vs. 17.9%, p=0.0207), although there was no statistical significance when the DLBCL cases were analyzed (56.6% vs. 22.2%, p=0.1530). CONCLUSIONS: These findings suggest that sIgL-negative B-NHL cases predominantly developed DLBCL in advanced disease, but were heterogeneous at the molecular level.

Association of promyelocytic leukemia protein with expression of IL-6 and resistance to treatment in multiple myeloma.

BACKGROUND/AIMS: Promyelocytic leukemia protein (PML) was originally identified as a tumor suppressor but has been recently shown to have the ability to control stem cell function in multiple tissues including malignancies. This study aimed to evaluate the biological and clinical significance of PML in multiple myeloma (MM). METHODS: We knocked down PML in myeloma cells with a lentiviral vector expressing microRNA to target PML, which were used for in vitro analyses. We also evaluated the association between PML expression in the bone marrow and patients' clinical parameters. RESULTS: The expression of IL-6 was decreased in myeloma cells with knocked-down PML expression. Immunohistochemical study showed that the PML expression level varied widely in the bone marrow of 48 MM patients, and that IL-6 expression correlated with PML expression in these patients. In addition, MM with high PML expression at diagnosis showed a poor prognosis regarding the 2-year survival, and PML and IL-6 positivity increased with the progression of disease in 13 sequentially analyzed cases. CONCLUSIONS: These results suggest that PML expression was positively associated with IL-6 expression in patients and was also related to tumor development and resistance to treatment in MM.

A case of acquired aplastic anemia with repeated cerebral infarctions at the beginning of immunosuppressive therapy.

Acquired aplastic anemia is a rare hematopoietic stem-cell disorder that results in pancytopenia and hypocellular bone marrow. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. Acquired aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy such as antithymocyte globulin or cyclosporine. We present a rare case report of a 68-year old patient with acquired severe aplastic anemia with repeated cerebral infarctions at the beginning of immunosuppressive therapy. He started immunosuppressive drug therapy with antithymocyte globulin and cyclosporine. During follow-up, magnetic resonance imaging revealed high signals at right thalamus and right pons by diffusion-weighted image. He was diagnosed with repeated cerebral infarctions of right thalamus and right pons. We successfully managed cerebral infarctions by frequent transfusions, edaravone administration, keeping the trough of serum cyclosporine (CsA) concentration around lower limit. This is the first report of successful management of acquired aplastic anemia with repeated cerebral infarctions.