Translocation of the BCL2 gene on the chromosome band 18q21.3 results in consistent expression of the Bcl2 protein, an apoptosis inhibitor. BCL2 usually translocates to the immunoglobulin (IG) heavy ...chain (IGH) gene as t(14;18)(q32;q21.3) and rarely to IG light chain (IGK, IGL) loci as t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). The t(14;18) translocation is observed in 70-95% of follicular lymphoma cases and 20-30% of diffuse large B-cell lymphoma (DLBCL) cases. The MYC gene on chromosome band 8q24 acts as an accelerator of cell proliferation. MYC translocates to 14q32/IGH as t(8;14)(q24;q32) or less commonly to 2p11/IGK as t(2;8)(p11;q24) or 22q11/IGL as t(8;22)(q24;q11). The 8q24/MYC translocation is detected in nearly all Burkitt lymphoma (BL) and up to 10% of DLBCL cases. Both translocations rarely occur in an identical cell and this lymphoid malignancy is termed BCL2 and MYC dual-hit lymphoma/leukemia (DHL). The pathological diagnosis in most cases of DHL with BCL2-IG and MYC-IG translocation is B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, although DLBCL is most common in DHL with BCL2-IG and MYC-nonIG translocation. The frequency of DHL with BCL2 and MYC translocation is estimated at around 2% of all B-cell malignancies. The condition is characterized by elevated serum lactate dehydrogenase levels, the presence of B symptoms, bone marrow involvement, advanced disease stage, extranodal involvement, and central nervous system (CNS) involvement at presentation or disease progression. Despite treatment strategies including CNS-targeted therapy, the prognosis for DHL is extremely poor. In this review, the current knowledge of the clinicopathological status of DHL is summarized and discussed. J Clin Exp Hematopathol 51(1) : 7-12, 2011
A novel fabrication process for a vertical wavy structured stretchable piezoelectric sensor combining dip coating and micro-corrugation process is proposed. By changing the dip coating withdrawal ...speed, the thickness of PVDF-TrFE (poly(vinylidene fluoride-trifluoroethylene)) films deposited on metal foils was controlled; the wave shape fabricated by the micro-corrugation process was influenced by the PVDF-TrFE film thickness. By reducing the PVDF-TrFE film thickness to less than 5 μm, the wave shape exhibited a high aspect ratio (wave height divided by wave pitch). From estimations obtained by measuring the change in substrate length before and after the microcorrugation process, the predicted stretchability is expected to be greater than 30%. The fabricated vertical wavy structured piezoelectric sensor with a PVDF-TrFE film thickness of approximately 2 μm showed more than 50% stretchability. The fabricated sensor was used as a finger-bending sensor for a virtual reality system, and the proposed process is a promising method for fabricating stretchable sensors.
We propose the use of a specially designed polyurethane foam with a plateau region in its mechanical characteristics-where stress remains nearly constant during deformation-between the ...electromyography (EMG) electrode and clothing to suppress motion artifacts in EMG measurement. Wearable EMG devices are receiving attention for monitoring muscle weakening due to aging. However, daily EMG measurement has been challenging due to motion artifacts caused by changes in the contact pressure between the bioelectrode and the skin. Therefore, this study aims to measure EMG signals in daily movement environments by controlling the contact pressure using polyurethane foam between the bioelectrode on the clothing and the skin. Through mechanical calculations and finite element method simulations of the polyurethane foam's effect, we clarified that the characteristics of the polyurethane foam significantly influence contact pressure control and that the contact pressure is adjustable through the polyurethane foam thickness. The optimization of the design successfully controlled the contact pressure between the bioelectrode and skin from 1.0 kPa to 2.0 kPa, effectively suppressing the motion artifact in EMG measurement.
We propose an e-textile bioelectrode array that consists of screen-printed silver paste wiring, a thermoplastic polyurethane insulation layer, and ionic liquid gel-embedded knit textile pads for ...wearable whole-body medical and healthcare monitoring. The technical challenges in integrating bioelectrodes onto knit textile include forming an insulation layer on silver paste wiring and fixing an ionic liquid gel on the wiring since the screen-printed silver paste wiring is removed by the organic solvent in conventional insulation ink and the adhesive force between the wiring and ionic liquid gel is weak. Our proposed e-textile bioelectrode array structure includes a laser-patterned hot-melt urethane film thermally attached to silver paste wiring on a polyurethane film and fabric to avoid wiring disconnection. An ionic liquid gel is formed and fixed in the conductive polymer-coated knit textile pad, which is fixed to an electrode with a hot-melt urethane film to improve the adhesive force. A <inline-formula> <tex-math notation="LaTeX">6\times3 </tex-math></inline-formula> bioelectrode array of 1 cm 2 ionic liquid gel pads is fabricated for electromyography. The impedance between the electrode and skin is 1 <inline-formula> <tex-math notation="LaTeX">\text{k}\Omega </tex-math></inline-formula> at 1 kHz, which is the same as that of a medical electrode. The adhesive force of the ionic liquid gel to the wiring is improved to 10 N. Finally, the erector spinae muscles are measured with our e-textile bioelectrode array, and the distribution of the flexion relaxation phenomenon can be measured to investigate back pain, leading to a medical diagnosis for plastic surgery or other divisions and healthcare applications.
Initial staging by positron emission tomography/computed tomography (PET/CT) scanning is recommended for patients with diffuse large B-cell lymphoma (DLBCL). Whether both PET/CT and bone marrow ...biopsy (BMB) are required remains unclear. This study examined whether staging by PET/CT is sufficient. Participants with untreated DLBCL assessed using both PET/CT and BMB were included. Patients received independent diagnostic assessments from a radiologist and a hematopathologist. Both hematoxylin–eosin staining and CD20 immunostaining were performed to determine the bone marrow involvement in BMB. A total of 84 patients were included. The number of patients with positive bone marrow involvement identified by PET/CT and BMB was 16 (19%) and 22 (26%), respectively. Eight (10%) patients showed positive results in both tests. When considering BMB as a reference, PET/CT showed 36% sensitivity and 87% specificity, with positive and negative predictive values of 50% and 79%, respectively. BMB-positive patients had shorter progression-free (PFS) and overall (OS) survival than their BMB-negative counterparts. Compared to PET/CT-negative patients, patients with positive results did not show any significant differences in PFS and OS. However, among 16 PET/CT-positive patients, poor PFS and OS were observed among patients who were also BMB positive. BMB remains a mandatory step in staging of untreated DLBCL patients.
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) −/+ rituximab (R) is the standard chemotherapeutic regimen for aggressive lymphoma, but is insufficient for aggressive lymphoma ...with adverse prognostic factors. Dose-adjusted (DA)-EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisolone) −/+ R demonstrates excellent efficacy against some aggressive lymphoma. Thus, we conducted a retrospective study to evaluate the feasibility and efficacy of this therapy in clinical practice. We enrolled 149 patients from 17 institutions diagnosed between 2007 and 2015. The median follow-up period for survivors was 27 months (range 0.2–123). The complete response (CR) rate of newly diagnosed patients was 79% (95% CI 68–87%). All patients were hospitalized to receive this therapy and 94% of patients also received granulocyte-colony-stimulating factor support. There were no treatment-related deaths. Febrile neutropenia (FN) and grade 3 or 4 infection occurred in 55% and 28% of patients, respectively. There were no significant differences in FN or infection between young (≤ 65 years) and elderly patients (> 65 years). In newly diagnosed diffuse large B-cell lymphoma-not otherwise specified patients (
n
= 46), the CR rate was 80% (95% CI 64–91%) and the 2-year OS rate was 81% (95% CI 66–90%). In the present study, DA-EPOCH −/+ R exhibited excellent efficacy and feasibility for aggressive lymphoma.
Heme oxygenase (HO)‐1 has anti‐oxidative, anti‐inflammatory, and anti‐apoptotic activities. However, little is known about the regulation of HO‐1 in human primary acute myeloid leukemia (AML) cells. ...Here we investigated the expression of HO‐1 in primary and established AML cells as well as other types of leukemic cells and normal monocytes, and its regulatory mechanism by the transcriptional repressor, BTB and CNC homology 1 (Bach1), and the activator, nuclear factor erythroid‐derived 2 related factor 2 (Nrf2). Leukemic cell lines such as U937 expressed little HO‐1, whereas most freshly isolated AML cells and monocytes expressed substantial amounts of HO‐1, along with Bach1 and Nrf2. When U937 cells were treated with phorbol myristate acetate (PHA) or γ‐interferon, they significantly expressed both HO‐1 and Bach1, like primary AML cells. Treatment with lipopolysaccharide (LPS) enhanced HO‐1 expression in U937 cells but suppressed it in primary monocytes and PMA‐treated U937 cells. In HO‐1‐expressing cells, Bach1 was localized in the cytoplasm, but Nrf2 was localized in the nuclei. Chromatin immunoprecipitation assay of these cells revealed the preferential binding of Nrf2 over Bach1 to Maf‐recognition elements, the enhancer regions of the HO‐1 gene. The downregulation of the HO‐1 gene with siRNA increased a cytotoxic effect of an anticancer drug on primary AML cells, whereas the downregulation of Bach1 increased HO‐1 expression, leading to enhanced survival. These and other results show that Bach1 plays a critical role in regulating HO‐1 gene expression in AML cells and its expression suppresses their survival by downregulating HO‐1 expression. Thus, functional upregulation of Bach1 is a potential strategy for antileukemic therapy. (Cancer Sci 2010)
1 Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama;
2 Department of Pathology, Tokai University School of Medicine, Kanagawa;
3 ...Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo;
4 Department of Pathology, St. Marianna University School of Medicine, Kawasaki;
5 Department of Chemotherapy, Kanagawa Cancer Center, Yokohama;
6 Division of Hemato-oncology, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama;
7 Department of Hematology, Tokai University School of Medicine, Kanagawa;
8 Department of Hematology, Yokohama City University Medical Center, Yokohama;
9 Cancer Center, Ehime University Graduate School of Medicine, Ehime;
10 Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa;
11 Department of Internal Medicine, Okayama Red Cross General Hospital, Okayama;
12 Division of Hematology, Tenri Hospital, Nara and
13 Division of Hematology and Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
Correspondence: Naoto Tomita, M.D., Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan E-mail: cavalier{at}ch-yamate.dlenet.com
Background: Lymphoid neoplasm with 18q21.3/ BCL2 and 8q24/ MYC translocation to immunoglobulin ( IG ) genes as dual-hit lymphoma/leukemia is very rare and known to have a poor clinical outcome.
Design and Methods: To clarify the clinicopathological characteristics of this malignancy, we analyzed 27 cases of cytogenetically proven dual-hit lymphoma/leukemia.
Results: Dual-hit lymphoma/leukemia was diagnosed at presentation in 22 cases and at relapse or disease progression in 5 cases. At the time of diagnosis of dual-hit lymphoma/leukemia, extranodal involvement was found in 25 cases (93%) and central nervous system involvement occurred in 15 cases (56%). The median survival and 1-year survival rate of the 27 cases were only 6 months and 22%, respectively, after diagnosis of the dual-hit lymphoma/leukemia. Seven cases of triple-hit lymphoma/leukemia (dual-hit lymphoma/leukemia with 3q27/ BCL6 translocation) were included; the median survival of these patients was only 4 months from the diagnosis of the dual-hit lymphoma/leukemia. The duration of survival of the patients with a triple-hit malignancy was shorter than that of the other 20 cases of dual-hit lymphoma/leukemia ( p =0.02). The translocation partner of MYC subdivided the dual-hit cases into two groups; 14 cases of IGH and 13 cases of IGK/L . The MIB-1 index was investigated in 14 cases with aggressive B-cell lymphoma, and was higher in the group with MYC-IGH translocation (n=7) than in the MYC-IGK/L group (n=7) ( p =0.02). Overall survival was not different between the MYC-IGH translocation group (n=14) and the MYC-IGK or MYC-IGL translocation group (n=13).
Conclusions: Dual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC .
Key words: BCL2 , MYC , dual-hit lymphoma/leukemia.
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