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Detection of minimal residual disease (MRD) is increasingly used in the management of leukemia patients. A wide variety of methods have been developed and include technologies designed to detect residual malignant cells beyond the sensitivity of conventional approaches such as morphology and banding cytogenetics in leukemia. The choice of the best method depends on the biology of the individual malignancy, i.e. on the determination of specific markers which are useful to differentiate between leukemic cells and normal hematopoiesis in leukemic patients. These markers include leukocyte differentiation antigens, fusion transcripts, transcripts overexpressed by mutated or nonmutated genes, rearranged genes, and individual markers like polymorphic repetitive DNA sequences. The major technologies for MRD detection, their advantages and disadvantages and their clinical applications are discussed in this special issue - from 'bench to bedside'. Providing a comprehensive overview on the significance of MRD in the evaluation, treatment and follow-up of hematologic malignancies, it will be of great value to hematologists, researchers interested in leukemias and lymphomas as well as laboratory technicians.
This volume provides a concise yet comprehensive overview of minimal residual disease (MRD) testing. The text reviews the history of MRD testing, MRD testing for acute lymphoblastic leukemia/lymphoma, molecular diagnostics for MRD analysis in hematopoietic malignancies, the use of "difference from normal" flow cytometry in monitoring AML response, ML-DS for measurable residual disease detection, and advancements in next generation sequencing for detecting MRD. Written by experts in the field, Minimal Residual Disease Testing: Current Innovations and Future Directions is a valuable resource for hematologists, oncologists, pathologists, and radiologists on the variety of technologies available to detect MRD and how best to integrate these platforms into clinical practice.
This book provides a comprehensive and up-to-date review of all aspects of childhood Acute Lymphoblastic Leukemia, from basic biology to supportive care. It offers new insights into the genetic pre-disposition to the condition and discusses how response to early therapy and its basic biology are utilized to develop new prognostic stratification systems and target therapy. Readers will learn about current treatment and outcomes, such as immunotherapy and targeted therapy approaches. Supportive care and management of the condition in resource poor countries are also discussed in detail. This is an indispensable guide for research and laboratory scientists, pediatric hematologists as well as specialist nurses involved in the care of childhood leukemia.
Better therapy of acute leukemias depends ultimately on better understanding of the distinction between leukemic and normal progenitor cells. This hugely important new book describes the current knowledge of acute leukemia biology and discusses new classification systems that have arisen as a result of emerging insights into pathogenesis. Estey, Faderl and Kantarjian, who all work at the respected Anderson Cancer Center in Houston, Texas, USA, examine in detail advances in the treatment of particular types of acute leukemia. Their book also covers the management of acute leukemia in general as well as the development of new therapies. This book will be extremely useful to clinicians.
Since the original publication of Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Allogeneic hematopoietic stem cell transplantation (HSC) has undergone several fast-paced changes. In this second edition, the editors have focused on topics relevant to evolving knowledge in the field in order to better guide clinicians in decision-making and management of their patients, as well as help lead laboratory investigators in new directions emanating from clinical observations. Some of the most respected clinicians and scientists in this discipline have responded to the recent advances in the field by providing state-of-the-art discussions addressing these topics in the second edition. The text covers the scope of human genomic variation, the methods of HLA typing and interpretation of high-resolution HLA results. Comprehensive and up-to-date, Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Second Edition offers concise advice on today's best clinical practice and will be of significant benefit to all clinicians and researchers in allogeneic HSC transplantation.
"Ineffective hematopoiesis in bone marrow and peripheral cytopenias are features of bone marrow failure and related syndromes. These diseases can progress to myelodysplastic syndrome, acute myeloid leukemia, and other malignancies. Acute myeloid leukemia is a heterogeneous complex malignancy characterized by proliferating myeloblasts in the bone marrow and a diverse range of recurrent molecular aberrations that occur in many different combinations. More specifically, the authors explore the McDonough strain of feline sarcoma virus-related tyrosine kinase 3 receptor mutations present in about 30-35% of acute myeloid leukemia patients. The way in which the Wnt signaling pathway plays an important role in normal hematopoiesis and its deregulation associated with acute myeloid leukemia is also discussed. This compilation also explores the importance of residual leukemic cells in disease relapse prognosis, as the new definition of the European LeukemiaNet for complete remission includes minimal or measurable residual disease negativity. Mutations detected in patients with clonal hematopoiesis are addressed, including those which most commonly affect DNMT3A, ASXL1, TET2, JAK2, SF3B1, SRSF2, and TP53 genes that had previously been identified as drivers in various myeloid neoplasms. The authors provide an overview of the roles of extracellular vesicles in multiple myeloma, their capacity as emerging biomarkers, and implications for liquid biopsy for detection and monitoring. The penultimate study focuses on toll-like receptors, which play an essential role in the recognition of invading pathogens via specific microbial molecular motifs, forming a bridge between the innate and adaptive immune responses. In conclusion, this compilation explores PROTACs, proteolysis targeting chimeras, which mediate the degradation of proteins of interest by hijacking the activity of E3-ubiquitin ligases for POI polyubiquitination and subsequent degradation by proteasome"--
The field of hematopoietic stem cell transplantation is rapidly evolving. Realization that hematopoietic stem cells give rise to the immune compartment has resulted in clinical trials of hematopoietic stem cell transplantation for patients with autoimmune diseases. Allogeneic hematopoietic transplants are a form of adoptive immunotherapy resulting in beneficial graft versus tumor effects. Large numbers of hematopoietic cells can be collected with ease. Therefore, a renewable source of cells for ex vivo genetic manipulations is readily available. Multiple trials combining hematopoietic transplants and gene therapy are in progress. One such application is the infusion of allogeneic lymphocytes containing a suicide gene to abort graft versus host disease. Hematopoietic stem cell transplantation is in reality the clinical and practical application of cellular therapy. Hematopoietic transplant physicians are by design or by practical application evolving into cell and gene therapy specialists. The excitement and enthusiasm in hematopoietic transplantation is that it offers a door to the future. A future not of drugs or titrating poisonous chemotherapy but rather of cellular and gene therapy. 1 ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FOR HEMATOLOGIC DISEASES Martin Korbling University o/Texas MD. Anderson Cancer Center, Houston, Texas 77030 INTRODUCTION Circulating hematopoietic stem cells have emerged as an alternative to bone marrow (BM) stem cells for allografting. For many years the reconstitutive potential of circulating stem cells was questioned; peripheral blood stem cells (PBSC) were even characterized a waste product (1).