Abstract : Next generation sequencing (NGS) technology has revealed the heterogeneity of diffuse large B-cell lymphoma (DLBCL) from a mutation perspective. Accordingly, the conventional cell of origin-based classification of DLBCL has changed to a mutation-based classification. Mutation analysis delineates that B-cell receptor pathway activation, EZH2 mutation, and NOTCH mutations are distinctive drivers of DLBCL. Moreover, the combination of RNA expression data and DNA mutation results suggests similarity between DLBCL subtypes and other non-Hodgkin lymphomas. NGS-based dissection of DLBCL would be the cornerstone for precision treatment in this heterogeneous disease in the near future.
Abstract : Plasma cell leukemia (PCL) is a rare and highly aggressive plasma cell neoplasm developing in 0.5?4% of patients with multiple myeloma (MM). The diagnostic criteria were recently revised from 20% to ≥5% of circulating plasma cells in peripheral blood smears. PCL is classified as primary or secondary; primary PCL is when it presents in patients with no MM. Primary PCL shows clinical and laboratory features at presentation that differ from MM and exhibits a dismal prognosis even with the use of effective agents against MM. Therefore, intensive chemotherapy should be initiated immediately after diagnosis, and autologous stem cell transplantation is recommended for transplant-eligible patients. Maintenance therapy after transplantation may reduce the rate of early relapses. We reviewed the definitions of PCL, revised diagnostic criteria, clinical features, and appropriate initial treatments for primary PCL.
Abstract : Mycosis fungoides (MF) and Sézary syndrome (SS) are a distinct disease entity of cutaneous T-cell lymphoma with heterogenous clinical features and prognosis. MF mainly involves skin and usually shows an indolent and favorable clinical course. In patients with advanced-stage disease, extracutaneous involvement including lymph nodes, viscera, and blood, or large cell transformation may be observed. SS is a leukemic form of advanced-stage MF, characterized by generalized erythroderma. Early-stage MF can be treated with skin-directed therapy. However, patients with refractory or advanced-stage disease are associated with severe symptoms or poor prognosis, requiring systemic therapy. Recent progress in understanding the pathogenesis of MF/SS has contributed to advances in the management of these rare diseases. This review aims to describe the clinical manifestations, diagnosis, risk stratification, and treatment strategy of MF/SS, focusing on the recent updates in the management of these diseases.
Abstract : Next-generation sequencing (NGS) allows high-throughput detection of molecular changes in tumors. Over the past 15 years, NGS has rapidly evolved from a promising research tool to a core component of the clinical laboratory. Sequencing of tumor cells provides an important step in detecting somatic driver mutations that not only characterize the disease but also influence treatment decisions. For patients with hematologic malignancies, NGS has been used for accurate classification and diagnosis based on genetic alterations. The recently revised World Health Organization classification and the European LeukemiaNet recommendations for acute myeloid leukemia consider genetic abnormalities as a top priority for diagnosis, prognostication, monitoring of measurable residual disease, and treatment choice. This review aims to present the role and utility of various NGS approaches for the diagnosis, treatment, and follow-up of hemato-oncology patients.
Guido D'Angelo
Blood Res 2013; 48(1): 10-15Abstract : This review summarizes the central role of hepcidin in the iron homeostasis mechanism, the molecular mechanism that can alter hepcidin expression, the relationship between hepcidin and erythropoiesis, and the pathogenetic role of hepcidin in different types of anemia. In addition, the usefulness of hepcidin dosage is highlighted, including the problems associated with analytical methods currently used as well as the measures of its molecular isoforms. Considering the central role of hepcidin in iron arrangement, it is reasonable to ponder its therapeutic use mainly in cases of iron overload. Further clinical trials are required before implementation.
Ayako Yumine, Stuart T. Fraser, and Daisuke Sugiyama
Blood Res 2017; 52(1): 10-17Abstract : The production of red blood cells, termed erythropoiesis, occurs in two waves in the developing mouse embryo: first primitive erythropoiesis followed by definitive erythropoiesis. In the mouse embryo, both primitive and definitive erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave then migrates to the fetal liver, fetal spleen and fetal bone marrow as these organs form. The fetal liver serves as the major organ for hematopoietic cell expansion and erythroid maturation after mid-gestation. The erythropoietic niche, which expresses critical cytokines such as stem cell factor (SCF), thrombopoietin (TPO) and the insulin-like growth factors IGF1 and IGF2, supports hematopoietic expansion in the fetal liver. Previously, our group demonstrated that DLK1+ hepatoblasts support fetal liver hematopoiesis through erythropoietin and SCF release as well as extracellular matrix deposition. Loss of DLK1+ hepatoblasts in
Negin Shokrgozar, and Habib Allah Golafshan
Blood Res 2019; 54(1): 10-16Abstract : Iron deficiency anemia and anemia of chronic disorders are the most common types of anemia. Disorders of iron metabolism lead to different clinical scenarios such as iron deficiency anemia, iron overload, iron overload with cataract and neurocognitive disorders. Regulation of iron in the body is a complex process and different regulatory proteins are involved in iron absorption and release from macrophages into hematopoietic tissues. Mutation in these regulatory genes is the most important cause of iron refractory iron deficiency anemia (IRIDA). This review provides a glance into the iron regulation process, diseases related to iron metabolism, and appropriate treatments at the molecular level.
Yoon Seok Choi
Blood Res 2020; 55(S1): S58-S62Abstract : Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma primarily involving the brain, spinal cord, or leptomeninges. PCNSL is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation has improved the survival outcome, together with reduced neurotoxicity. Recent studies found that aberrant activation of the B-cell receptor-signaling pathway and activation of the NF-κB are frequent genetic alterations and could be good targets for the treatment of PCNSL. Herein, we have reviewed the current status and recent advances in the biology and management of PCNSL.
Abstract : The goal of cancer immunotherapy is to restore and optimize the immune response against malignant clones through several stages, from recognition of tumor antigens to establishment of long-lived memory cell populations. Boosting the intrinsic anti-tumor immune responses of the patients’ own, several types of “active immunotherapies” have been tried in many types of malignancies, inspired by successful experiences of immune checkpoint inhibition even in Hodgkin lymphoma. However, in B-cell non-Hodgkin lymphomas, clinical usefulness of such “active immunotherapies” is relatively unsatisfactory considering the remarkable advances in “passive immunotherapy,” including CD19-targeting chimeric antigen receptor T-cell therapy. Understanding how tumor cells and immune cells interact and contribute to immune evasion processes in the tumor microenvironment (TME) is an important prerequisite for the successful restoration of anti-tumor immune responses. In this review, a recent understanding of the biology of the immune tumor microenvironment surrounding B-cell non-Hodgkin lymphomas will be introduced. In addition, novel therapeutic approaches targeting the immune microenvironment other than immune checkpoint blockade are discussed.
Abstract : Immunohistochemistry is a technique that uses antigen-antibody interactions to detect specific proteins in cells. This technique has several essential applications in lymphoma diagnosis, including identifying the cell lineage and phase of maturation, detecting specific genetic alterations, visualizing the degree of cell proliferation, and identifying therapeutic targets. CD3 is a pan T-cell marker expressed on most of the mature T/NK-cell lymphomas, except for anaplastic large cell lymphoma, whereas CD20 is a pan B-cell marker that is expressed on most of the mature B-cell lymphomas. CD79a may be a good alternative to CD20, compensating for its loss owing to the plasmocytic differentiation of tumor cells or history of rituximab administration. CD56, a neuroendocrine marker, is used as an NK cell marker in lymphoma diagnosis. Characteristic translocations occurring in follicular lymphoma (BCL2) and mantle cell lymphoma (CCND1) can be detected by the overexpression of Bcl-2 and cyclin D-1 in immunohistochemistry, respectively. Ki-67 reflects the degree of tumor cell proliferation by indicating cells in cell cycle phases other than G0. With the development of immunotherapy, several antibodies against markers such as programmed death-ligand 1 (PD-L1), CD19, and CD30 have been used as biomarkers to identify therapeutic targets. It is critical to properly fix the specimens to obtain accurate immunohistochemical results. Therefore, all processes, from tissue collection to the final pathological diagnosis, must be performed appropriately for accurate lymphoma diagnosis.
Christopher Chin Keong Liam, Jim Yu-Hsiang Tiao, Yee Yee Yap, Yi Lin Lee, Jameela Sathar, Simon McRae, Amanda Davis, Jennifer Curnow, Robert Bird, Philip Choi, Pantep Angchaisuksiri, Sim Leng Tien, Joyce Ching Mei Lam, Doyeun Oh, Jin Seok Kim, Sung-Soo Yoon, Raymond Siu-Ming Wong, Carolyn Lauren, Eileen Grace Merriman, Anoop Enjeti, Mark Smith, Ross Ian Baker
Blood Res 2023;58: 36-41Dong Wook Jekarl, Jae Kwon Kim, Jay Ho Han, Howon Lee, Jaeeun Yoo, Jihyang Lim, Yonggoo Kim
Blood Res 2023;58: S1-S7Yoo Jin Lee, Youjin Kim, Sang Hyuk Park, Jae-Cheol Jo
Blood Res 2023;58: S90-S95Eun-Ji Choi
Blood Res 2023;58: S29-S36+82-2-516-6582