Angiogenesis in hematologic malignancies

Angiogenesis is defined as the formation of new capillaries from preexisting blood vessels and plays an important role in the progression of solid tumors. Recently a similar relationship has been described in several hematologic malignancies. Expression of the angiogenic peptides vascular endothelial growth factor (VEGF) and basic fibroblast growth factor correlates with clinical characteristics in leukemia and non-Hodgkin's-lymphoma and the serum/plasma concentrations serve as predictors of poor prognosis. Increased bone marrow microvessels in multiple myeloma (MM) are correlated with decreased overall survival. Thalidomide which has antiangiogenic effects and direct cytotoxic effects was found to be effective in MM, myelodysplastic syndrome and acute myeloid leukemia (AML). Preliminary data indicate activity of VEGF-tyrosine kinase inhibitors in AML. Clinical research is now aimed at testing antiangiogenic treatment strategies in several hematologic neoplasms as well as identifying the best candidate patients for specific approaches.     

Angiogenesis in hematologic malignancies

Angiogenesis, defined as the blood vessel generation from preexisting blood vessels, was found to play an important role in the progression of solid tumors. In addition, bone marrow-derived endothelial precursor cells may contribute to tumor angiogenesis. Recently angiogenesis induction was described in several hematologic neoplasms as leukemia, lymphoma, myelodysplastic syndrome and multiple myeloma (MM). Clinical angiogenesis research also termed as angiodiagnosis has established the prognostic relevance of markers of angiogenesis e.g., microvessel density and circulating levels of angiogenic peptides. Development of antiangiogenic treatment for hematologic neoplasms has recently been sparked by the success of Thalidomide (Thal) which has antiangiogenic properties in MM. Antiangiogenic treatment strategies are now being tested in clinical trials on several types of hematologic neoplasms.     

MicroRNAs in hematological malignancies

MicroRNAs (miRNAs) have become one of the hottest topics in biology over recent years, but remarkably have only been formally recognized for just over 10 years. These endogenously produced short (19–24 nt) non-coding RNAs have introduced an entirely new paradigm in our understanding of gene control and it is now evident that miRNAs play a crucial regulatory role in many, if not all, physiological and pathological processes. In this review we provide an overview of the role and potential clinical utility for miRNAs in hematological malignancies and their function in normal hematopoiesis. Although still in its infancy, the miRNA field has already added much to our understanding of hematological processes, and provides us with novel tools as both biomarkers and therapeutic agents for hematological malignancies.     

DC-based immunotherapy for hematological malignancies

Great advances have been made in the treatment of hematological malignancies, but achieving a definitive cure remains an elusive goal for the majority of patients. Antigen-specific tumor immunotherapy has the potential to improve clinical outcome in patients with such diseases by eradicating chemotherapy-resistant tumor cell clones without damaging normal tissues. Dendritic cells (DCs) serve as an essential link between the innate and the adaptive immune systems, acting as key controllers of antigen-specific T cell responses. Molecular identification of tumor-specific antigens recognized by T lymphocytes and technical advances in ex vivo generation of human DCs has enabled us to develop DC-based tumor immunotherapies (also called “DC vaccines”). To date, a large number of clinical trials of DC vaccines have been conducted for a variety of tumors, including hematological malignancies. Overall, these trials have demonstrated that DC vaccines have excellent safety profiles, moderate immunological activity, and mild clinical efficacy. To establish a role for DC vaccines in the treatment of hematological malignancies, we need both to define patient populations that can obtain clinical benefit from DC vaccines and to develop combination therapies that augment clinical efficacy of DC vaccines. In this review, I will describe current status of DC-based immunotherapy for hematological malignancies, and discuss future perspectives in this field.     

Vitamin D in hematological disorders and malignancies

Commonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in hematological cancer pathogenesis and shows promise as an anti‐cancer therapy. Serum levels of 25(OH)D₃, the precursor to the active form of vitamin D, calcitriol, are frequently lower in patients with hematological disease compared to healthy individuals. This often correlates with worse disease outcome. Furthermore, diseased cells typically highly express the vitamin D receptor, which is required for many of the anti‐cancer effects observed in multiple in vivo and in vitro cancer models. In abnormal hematological cells, vitamin D supplementation promotes apoptosis, induces differentiation, inhibits proliferation, sensitizes tumor cells to other anti‐cancer therapies, and reduces the production of pro‐inflammatory cytokines. Although the dosage of vitamin D required to achieve these effects may induce hypercalcemia in humans, analogs and combinatorial treatments have been developed to circumvent this side effect. Vitamin D and its analogs are well tolerated in clinical trials, and thus, further investigation into the use of these agents in the clinic is warranted. Here, we review the current literature in this field.     

Angiogenesis and antiangiogenic therapy in hematologic malignancies

Angiogenesis, the generation of new blood capillaries from preexisting blood vessels, is tightly regulated in the adult organism. Although many of the initial studies were performed on solid tumors, increasing evidence indicates that angiogenesis also plays an important role in hematologic malignancies. Overexpression of angiogenic factors in particular VEGF and bFGF in most hematologic malignancies may explain the increased angiogenesis found in these malignancies and correlate with poor prognosis as well as decreased overall survival. In this review, we focus on the current literature of angiogenesis and antiangiogenic therapy in hematologic malignancies, and finally describe advances and potential challenges in antiangiogenic treatment in hematologic malignancies.     

Serum cholesterol and triglycerides in hematological malignancies

Serum levels of total cholesterol and triglycerides were studied in 202 patients affected by various hematological malignancies at the time of diagnosis. A hypocholesterolemia was found in 44% of patients affected by lymphoproliferative diseases and acute lymphoblastic leukemia, with an evident correlation with the clinical stage (5.7% of patients in nonadvanced stages, 67.8% in advanced stages). In acute and chronic myeloproliferative diseases, the overall incidence of hypocholesterolemia was 71%. In particular, a greater incidence of low cholesterol values was found in chronic myeloid leukemia and in idiopathic myelofibrosis than in polycythemia vera. No significant correlation was found in this group of diseases between the values of cholesterol and the main hematological parameters studied (WBC, number of circulating blasts, degree of splenomegaly, levels of hemoglobin, hematocrit). The incidence of significant alterations of triglycerides appeared negligible. It is thus possible to affirm that hypocholesterolemia constitutes an interesting biological aspect in hematological malignancies, and that total cholesterol could represent a parameter, even though secondary, in the follow-up of hematological neoplastic pathologies.     

Management of hematological malignancies during pregnancy

The management of hematological malignancies during pregnancy is a challenging endeavor, which not only requires technical skills and knowledge by the clinicians but also requires sound clinical judgment and compassion, keeping in mind the patient and family preferences and, ultimately, the wellbeing of the neonate. The incidence of hematological malignancies during pregnancy is rare, ranging from 1 in 1,000 to 1 in 10,000 deliveries, impeding the design and execution of large prospective studies. The purpose of this review is to evaluate the limited existing data and make useful suggestions in the management of acute and chronic leukemias, Hodgkin and non‐Hodgkin lymphomas, plasma cell myeloma, and other hematological malignancies, such as myelodysplastic syndromes and hairy cell leukemia, during pregnancy. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Bridging the gap in hematological malignancies

After the success of the BTG Series in Singapore in 2010 and 2011, meeting organizers held the 3rd International Hematologic Malignancies Conference in Hong Kong. Held on 23-25 February, the BTG meeting provided an opportunity to further scientific discourse in the Asia-Pacific region. Featuring the world-renowned medical faculty and an abundance of discussion forums, the conference provided attendees the opportunity to interact with field leaders and exposed them to the latest research. The BTG conferences focus on hematologic malignancies, especially leukemia, lymphoma and myeloma. The BTG series provides an exceptional platform for the exchange of ideas for the Asia-Pacific hematology oncology healthcare community. It offers many novel opportunities for practicing physicians as well as fellows in training to meet with the world thought leaders. The annual conference brings together key opinion leaders from the Asia-Pacific region, the USA and Europe. The underlying motto is to bring the continents together and generate a global community in the quest against cancer. BTG recognizes the contributions of the Asia-Pacific physicians who are among the world leaders and gives the younger generation opportunities to present their work in a world arena.     

Newer monoclonal antibodies for hematological malignancies

Since the approval of rituximab in 1997, monoclonal antibodies have come to play an important role in the therapy of hematological malignancies. Rituximab, gemtuzumab ozogamicin, and alemtuzumab are US Food and Drug Administration-approved for treatment of B-cell lymphomas, acute myeloid leukemia, and chronic lymphocytic leukemia, respectively. Multiple monoclonal antibodies directed against new and not-so-new cellular antigens are undergoing development and investigation all over the world. Most of these new compounds have undergone primatization or humanization, improving their specificity and decreasing their antigenicity when compared to earlier murine or chimeric products. This review will focus on three major aspects of monoclonal antibody therapy: 1) new therapeutic approaches with currently approved agents; 2) preclinical and clinical experience accumulated on new agents in the last few years; discussion will include available phase I, II, and III data on ofatumumab, epratuzumab, CMC-544, HeFi-1, SGN-30, MDX-060, HuM195 (lintuzumab), galiximab, lumiliximab, zanolimumab, and apolizumab; and 3) the role of naked and radiolabeled monoclonal antibodies in the hematopoietic stem cell transplantation setting.     

血液恶性肿瘤感染的临床特点和治疗进展

近年来,随着新的免疫治疗、靶向治疗和大剂量化疗方案的开展,明显改善了血液恶性肿瘤患者的缓解率和生存率。但同时这些治疗导致了患者免疫系统的严重抑制,大剂量化疗使患者的粒细胞缺乏（粒缺）期延长。因此,感染成为血液恶性肿瘤患者越来越突出的问题,甚至成为这些患者死亡的主要原因。