Pub Date : 2018-06-27DOI: 10.5772/INTECHOPEN.76588
B. Inusa, Lodi Mariachiara, P. Giovanni, Kenneth I.Ataga
Sickle cell nephopathy (SCN) begins early in childhood from failure of urinary concen- tration (hyposthenuria), albuminuria to hyperfiltration, hematuria and progression to falling glomerular filtration to end-stage renal disease and increased mortality. Renal involvement is more severe in homozygous individuals (HbSS) than in compound het-erozygous patients (HbSC). The pathogenesis of SCN is multifactorial from hypoxia, acidosis, hemolysis, ischemia-reperfusion injury and albuminuria. The clinical manifes tations depend on whether the main pathology is tubular, glomerular or a mixture of both abnormalities. This chapter offers a critical review of the recent literature and will highlight the pathophysiology, epidemiology, clinical manifestations and management of sickle cell nephropathy with particular focus on the major advance in the early diagnosis. Learning points : For SCN, the onset of hyperfiltration and albuminuria in infants and childhood is an opportunity to intervene early. There is no diagnostic markertest capable of detecting the onset of these changes. Moreover there is no reliable therapeutic agent to prevent or halt early changes due to SCN. The development of a marker of renal impair - ment in SCD such as such as Cystatin C assay if validated may be appropriate for wider clinical application.
{"title":"Sickle Cell Nephropathy: Current Understanding of the Presentation, Diagnostic and Therapeutic Challenges","authors":"B. Inusa, Lodi Mariachiara, P. Giovanni, Kenneth I.Ataga","doi":"10.5772/INTECHOPEN.76588","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76588","url":null,"abstract":"Sickle cell nephopathy (SCN) begins early in childhood from failure of urinary concen- tration (hyposthenuria), albuminuria to hyperfiltration, hematuria and progression to falling glomerular filtration to end-stage renal disease and increased mortality. Renal involvement is more severe in homozygous individuals (HbSS) than in compound het-erozygous patients (HbSC). The pathogenesis of SCN is multifactorial from hypoxia, acidosis, hemolysis, ischemia-reperfusion injury and albuminuria. The clinical manifes tations depend on whether the main pathology is tubular, glomerular or a mixture of both abnormalities. This chapter offers a critical review of the recent literature and will highlight the pathophysiology, epidemiology, clinical manifestations and management of sickle cell nephropathy with particular focus on the major advance in the early diagnosis. Learning points : For SCN, the onset of hyperfiltration and albuminuria in infants and childhood is an opportunity to intervene early. There is no diagnostic markertest capable of detecting the onset of these changes. Moreover there is no reliable therapeutic agent to prevent or halt early changes due to SCN. The development of a marker of renal impair - ment in SCD such as such as Cystatin C assay if validated may be appropriate for wider clinical application.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"389 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116765023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-27DOI: 10.5772/INTECHOPEN.76849
G. Balatzenko, M. Guenova
During the past two decades, hematological disorders have been extensively studied by means of classical laboratory approaches, for example, microscopy, immunophenotyping, clinical chemistry, genetic diagnostic tests such as conventional cytogenetics, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR), as well as by high-throughput technologies, including microarray-based platforms for the global analysis of DNA alterations (single nucleotide polymorphism (SNP); array, comparative genomic hybridization (CGH)), gene expression profiling (GEP), next-generation sequencing (NGS), digitalized imaging, and so on. Systemic application of these techniques has allowed for the refinement of the molecular mechanisms involved in the pathological transformation of hematopoietic stem/progenitor cells and disease progression in a number of hematological disorders. More importantly, they have permitted more precise and reproducible diagnoses of the different entities, risk stratification of patients, and treating them in the most appropriate manner with tailored therapeutic strategies.
{"title":"Introductory Chapter: Hematology in Times of Precision and Innovation","authors":"G. Balatzenko, M. Guenova","doi":"10.5772/INTECHOPEN.76849","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76849","url":null,"abstract":"During the past two decades, hematological disorders have been extensively studied by means of classical laboratory approaches, for example, microscopy, immunophenotyping, clinical chemistry, genetic diagnostic tests such as conventional cytogenetics, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR), as well as by high-throughput technologies, including microarray-based platforms for the global analysis of DNA alterations (single nucleotide polymorphism (SNP); array, comparative genomic hybridization (CGH)), gene expression profiling (GEP), next-generation sequencing (NGS), digitalized imaging, and so on. Systemic application of these techniques has allowed for the refinement of the molecular mechanisms involved in the pathological transformation of hematopoietic stem/progenitor cells and disease progression in a number of hematological disorders. More importantly, they have permitted more precise and reproducible diagnoses of the different entities, risk stratification of patients, and treating them in the most appropriate manner with tailored therapeutic strategies.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"85 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114517558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-27DOI: 10.5772/INTECHOPEN.75141
V. Pilli
The circulatory system plays a vital role in the survival of an organism by supplying it with essential nutrients, signaling molecules and eliminating the waste or toxic products from the body. This flow is tightly regulated by various factors, procoagulants support the formation of hemostatic plugs to prevent the leakage or blood loss and anticoagulants prevent the formation of unwanted clots. Disruption or dysregulation of procoagulants and anticoagulants lead to clinical complexities. In this chapter defects in the coagulation system, hereditary, acquired coagulation disorders, their diagnosis and recent clinical modulators of the coagulation system are discussed.
{"title":"Understanding the Clotting Cascade, Regulators, and Clinical Modulators of Coagulation","authors":"V. Pilli","doi":"10.5772/INTECHOPEN.75141","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75141","url":null,"abstract":"The circulatory system plays a vital role in the survival of an organism by supplying it with essential nutrients, signaling molecules and eliminating the waste or toxic products from the body. This flow is tightly regulated by various factors, procoagulants support the formation of hemostatic plugs to prevent the leakage or blood loss and anticoagulants prevent the formation of unwanted clots. Disruption or dysregulation of procoagulants and anticoagulants lead to clinical complexities. In this chapter defects in the coagulation system, hereditary, acquired coagulation disorders, their diagnosis and recent clinical modulators of the coagulation system are discussed.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133851916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
More recently, DLBCL has witnessed advances in the molecular profiling and treatment of patients with refractory and relapsed disease. DLBCL is biologically and clinically a heterogeneous disease. Despite its aggressive behavior, DLBCL is a potentially curable disease with overall survival of 94 and 55% in patients with low and high rIPI scores, respectively. The combination of anti-CD 20 monoclonal antibody rituximab and cyclo- phosphamide, doxorubicin, oncovin (vincristine) and prednisone (R-CHOP) chemotherapy every 3 weeks is the first line treatment. Radiotherapy is reserved for the patients with bulky disease who fail to achieve complete remission after first line treatment. CNS prophylaxis is reserved for the patients with high lactate dehydrogenase (LDH) levels and involvement of more than one extranodal sites and for the patients with involvement of selective extranodal sites like testes and orbits (the sanctuary sites). Patients who suffer relapse after first line treatment receive high-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT). Variants of DLBCL like double-hit (presence of MYC and BCL2/BCL6) and triple-hit (presence of MYC, BCL2 and BCL6) lymphomas are treated differently and these patients have worse outcome. Several novel immunothera- peutic agents like checkpoint inhibitors and chimeric antigen receptor T cell (CART) are being investigated in randomized trials on patients with DLBCL. B cell lymphoma, double-hit lymphoma, update, triple-hit lymphoma, R CHOP, DA-R EPOCH B-progenitor cell into B cell. Mature B cells immunoglobulin VDJ gene rearrangement a complete IgM antibody molecule on the cell surface After release from the bone marrow, antigen naïve mature B cells are exposed to antigen in the interfollicular area of the secondary lymphoid tissues. Majority then migrate into the germinal center. Mature antigen exposed B cells prolif-erate in the center of a primary follicle to form the germinal center. The centroblasts mature into centrocytes as they transition into light zone of the germinal center. In the germinal center, B cell undergoes class-switch recombination and somatic hypermutation. Centroblasts are thought to give rise to germinal center B cell (GCB) DLBCL. After transition through the germinal center, B cells can become memory cells or plasmablasts which undergo further development to become plasma cells. Plasmablasts are to give rise to activated B cell like (ABC) DLBCL
{"title":"Recent Advances in Diffuse Large B Cell Lymphoma","authors":"Vivek Kumar, Sarvadaman Makardhwaj Shrivastava, TrishalaMeghal, Binod Abhinav Chandra","doi":"10.5772/INTECHOPEN.74263","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.74263","url":null,"abstract":"More recently, DLBCL has witnessed advances in the molecular profiling and treatment of patients with refractory and relapsed disease. DLBCL is biologically and clinically a heterogeneous disease. Despite its aggressive behavior, DLBCL is a potentially curable disease with overall survival of 94 and 55% in patients with low and high rIPI scores, respectively. The combination of anti-CD 20 monoclonal antibody rituximab and cyclo- phosphamide, doxorubicin, oncovin (vincristine) and prednisone (R-CHOP) chemotherapy every 3 weeks is the first line treatment. Radiotherapy is reserved for the patients with bulky disease who fail to achieve complete remission after first line treatment. CNS prophylaxis is reserved for the patients with high lactate dehydrogenase (LDH) levels and involvement of more than one extranodal sites and for the patients with involvement of selective extranodal sites like testes and orbits (the sanctuary sites). Patients who suffer relapse after first line treatment receive high-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT). Variants of DLBCL like double-hit (presence of MYC and BCL2/BCL6) and triple-hit (presence of MYC, BCL2 and BCL6) lymphomas are treated differently and these patients have worse outcome. Several novel immunothera- peutic agents like checkpoint inhibitors and chimeric antigen receptor T cell (CART) are being investigated in randomized trials on patients with DLBCL. B cell lymphoma, double-hit lymphoma, update, triple-hit lymphoma, R CHOP, DA-R EPOCH B-progenitor cell into B cell. Mature B cells immunoglobulin VDJ gene rearrangement a complete IgM antibody molecule on the cell surface After release from the bone marrow, antigen naïve mature B cells are exposed to antigen in the interfollicular area of the secondary lymphoid tissues. Majority then migrate into the germinal center. Mature antigen exposed B cells prolif-erate in the center of a primary follicle to form the germinal center. The centroblasts mature into centrocytes as they transition into light zone of the germinal center. In the germinal center, B cell undergoes class-switch recombination and somatic hypermutation. Centroblasts are thought to give rise to germinal center B cell (GCB) DLBCL. After transition through the germinal center, B cells can become memory cells or plasmablasts which undergo further development to become plasma cells. Plasmablasts are to give rise to activated B cell like (ABC) DLBCL","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133637300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-27DOI: 10.5772/INTECHOPEN.73675
C. Lantos, S. Kornblau, A. Qutub
Leukemia, a blood cancer originating in the bone marrow, presents as a heterogeneous disease with highly variable survival rates. Leukemia is classified into major types based on the rate of cancerous cell growth and cell lineage: chronic or acute and myeloid or lymphoid leukemia. Histological and cytological analysis of the peripheral blood and the bone marrow can classify these major leukemia categories. However, histological analyses of patient biopsies and cytological microscopic assessment of blood and bone marrow smears are insufficient to diagnose leukemia subtypes and to direct therapy. Hence, more expensive and time-consuming diagnostic tools routinely complement histological-cytological analysis during a patient ’ s diagnosis. To extract more accurate and detailed information from patient tissue samples, digital pathology is emerging as a powerful tool to enhance biopsy- and smear-based decisions. Furthermore, digital pathology methods integrated with advances in machine learning enable new diagnos- tic features from leukemia patients ’ histological and cytological slides and optimize patient classification, thus providing a cheaper, more robust, and faster diagnostic tool than current standards. This review summarizes emerging approaches to automatically diagnose leukemia from morphological and cytological-histological analyses.
{"title":"Quantitative-Morphological and Cytological Analyses in Leukemia","authors":"C. Lantos, S. Kornblau, A. Qutub","doi":"10.5772/INTECHOPEN.73675","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.73675","url":null,"abstract":"Leukemia, a blood cancer originating in the bone marrow, presents as a heterogeneous disease with highly variable survival rates. Leukemia is classified into major types based on the rate of cancerous cell growth and cell lineage: chronic or acute and myeloid or lymphoid leukemia. Histological and cytological analysis of the peripheral blood and the bone marrow can classify these major leukemia categories. However, histological analyses of patient biopsies and cytological microscopic assessment of blood and bone marrow smears are insufficient to diagnose leukemia subtypes and to direct therapy. Hence, more expensive and time-consuming diagnostic tools routinely complement histological-cytological analysis during a patient ’ s diagnosis. To extract more accurate and detailed information from patient tissue samples, digital pathology is emerging as a powerful tool to enhance biopsy- and smear-based decisions. Furthermore, digital pathology methods integrated with advances in machine learning enable new diagnos- tic features from leukemia patients ’ histological and cytological slides and optimize patient classification, thus providing a cheaper, more robust, and faster diagnostic tool than current standards. This review summarizes emerging approaches to automatically diagnose leukemia from morphological and cytological-histological analyses.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116537797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-06-27DOI: 10.5772/INTECHOPEN.78769
E. Andrès, R. Mourot-Cottet
In this chapter, we report and discuss the diagnosis and management of idiosyncratic drug-induced, or drug-associated, severe neutropenia, and agranulocytosis (neutrophil count of <0.5 × 10 9 /L). In this setting, neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis, with severe deep tissue infections (e.g., pneumonia), life-threatening infections, septicemia, and septic shock in two-thirds of all hospitalized patients. Recently, several poor prognostic factors, impacting the hemato- logical recovery, the duration of hospitalization, and the outcome have been identified that may be helpful when identifying “frailty” patients. These factors include: old age, poor performance status, septicemia or shock, comorbidities such as renal failure, and a neutrophil count below 0.1 × 10 9 /L. recovery. In this situation, modern management, with broad-spectrum antibiotics in case of any sepsis sign and hematopoietic growth factors (HGF) (particularly G-CSF), is likely to improve the prognosis, with a current mortality rate around 5%.
{"title":"Idiosyncratic Drug-Induced Severe Neutropenia and Agranulocytosis: State of the Art","authors":"E. Andrès, R. Mourot-Cottet","doi":"10.5772/INTECHOPEN.78769","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.78769","url":null,"abstract":"In this chapter, we report and discuss the diagnosis and management of idiosyncratic drug-induced, or drug-associated, severe neutropenia, and agranulocytosis (neutrophil count of <0.5 × 10 9 /L). In this setting, neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis, with severe deep tissue infections (e.g., pneumonia), life-threatening infections, septicemia, and septic shock in two-thirds of all hospitalized patients. Recently, several poor prognostic factors, impacting the hemato- logical recovery, the duration of hospitalization, and the outcome have been identified that may be helpful when identifying “frailty” patients. These factors include: old age, poor performance status, septicemia or shock, comorbidities such as renal failure, and a neutrophil count below 0.1 × 10 9 /L. recovery. In this situation, modern management, with broad-spectrum antibiotics in case of any sepsis sign and hematopoietic growth factors (HGF) (particularly G-CSF), is likely to improve the prognosis, with a current mortality rate around 5%.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127168497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-03-30DOI: 10.5772/INTECHOPEN.74931
Bhaskar Kahali
Myeloid sarcomas are extramedullary myeloid masses with associated tissue damage. Myeloid sarcomas usually arise before, during or after diagnosis of acute leukemia, most often AML. Majority of the patients with myeloid sarcoma respond to upfront systemic chemotherapy and sometimes bone marrow transplant, but it is unclear which patients will benefit from which treatments. This is primarily due to the paucity of knowledge on myeloid sarcoma. At present, there are no prognostic biomarkers for myeloid sarcoma, which can help in risk stratification in patients with myeloid sarcoma. Several studies have suggested that myeloid sarcoma is more likely to occur with certain translocations such as CBF and MLL rearrangements. In addition, sequencing analysis has identified several mutations in genes such as FLT3, NPM1, EZH2, and KIT. Nevertheless, there is still lack of knowledge to understand why particular leukemia migrates to the skin and soft tissues and becomes refractory to systemic therapy.
{"title":"Myeloid Sarcoma: The Other Side of Acute Leukemia","authors":"Bhaskar Kahali","doi":"10.5772/INTECHOPEN.74931","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.74931","url":null,"abstract":"Myeloid sarcomas are extramedullary myeloid masses with associated tissue damage. Myeloid sarcomas usually arise before, during or after diagnosis of acute leukemia, most often AML. Majority of the patients with myeloid sarcoma respond to upfront systemic chemotherapy and sometimes bone marrow transplant, but it is unclear which patients will benefit from which treatments. This is primarily due to the paucity of knowledge on myeloid sarcoma. At present, there are no prognostic biomarkers for myeloid sarcoma, which can help in risk stratification in patients with myeloid sarcoma. Several studies have suggested that myeloid sarcoma is more likely to occur with certain translocations such as CBF and MLL rearrangements. In addition, sequencing analysis has identified several mutations in genes such as FLT3, NPM1, EZH2, and KIT. Nevertheless, there is still lack of knowledge to understand why particular leukemia migrates to the skin and soft tissues and becomes refractory to systemic therapy.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131456550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.5772/INTECHOPEN.72652
S. Mithraprabhu, A. Spencer
Liquid biopsies represent an innovative methodology for cancer diagnostics and disease monitoring. The analysis of circulating cell-free nucleic acids (CFNA) and circulating tumour cells (CTC) are rapidly being adopted for quantitative and qualitative charac- terisation of the tumour genome and as a mode of non-invasive therapeutic monitoring. Circulating cell-free DNA (cfDNA) and CTC are representative of the underlying mutational profile of a cancer whereas the evaluation of extracellular RNA (exRNA) can be utilised as a prognostic biomarker thus providing critical biological information both at the time of diagnosis and during disease evolution. In this chapter, we will review the emerging utility of CFNA and CTC as biomarkers of prognosis and for both mutational characterisation and monitoring disease progression, and how these have the potential to provide additional information as an adjunct to bone marrow biopsies and conven - tional disease markers in multiple myeloma (MM). Emerging data suggest that liquid biopsies might offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognostication and therapeutic decision making in MM, with particular applicability in subsets of patients where conventional markers of disease burden may be less informative. cells are utilised for mutational characterisation, biomarker identification and to define disease burden. Peripheral blood can be utilised to obtain both CTC and CFNA. DNA and RNA can be derived from both sources and as both CTC and CFNA are derived from multiple tumour sites they theoretically will provide a more comprehensive profile of the disease in comparison to a single-site BM biopsy.
{"title":"Liquid Biopsy in Multiple Myeloma","authors":"S. Mithraprabhu, A. Spencer","doi":"10.5772/INTECHOPEN.72652","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72652","url":null,"abstract":"Liquid biopsies represent an innovative methodology for cancer diagnostics and disease monitoring. The analysis of circulating cell-free nucleic acids (CFNA) and circulating tumour cells (CTC) are rapidly being adopted for quantitative and qualitative charac- terisation of the tumour genome and as a mode of non-invasive therapeutic monitoring. Circulating cell-free DNA (cfDNA) and CTC are representative of the underlying mutational profile of a cancer whereas the evaluation of extracellular RNA (exRNA) can be utilised as a prognostic biomarker thus providing critical biological information both at the time of diagnosis and during disease evolution. In this chapter, we will review the emerging utility of CFNA and CTC as biomarkers of prognosis and for both mutational characterisation and monitoring disease progression, and how these have the potential to provide additional information as an adjunct to bone marrow biopsies and conven - tional disease markers in multiple myeloma (MM). Emerging data suggest that liquid biopsies might offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognostication and therapeutic decision making in MM, with particular applicability in subsets of patients where conventional markers of disease burden may be less informative. cells are utilised for mutational characterisation, biomarker identification and to define disease burden. Peripheral blood can be utilised to obtain both CTC and CFNA. DNA and RNA can be derived from both sources and as both CTC and CFNA are derived from multiple tumour sites they theoretically will provide a more comprehensive profile of the disease in comparison to a single-site BM biopsy.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"2015 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132674100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-12-20DOI: 10.5772/INTECHOPEN.72122
J. Sepulveda, Noé Seija, P. Oppezzo, Marcelo A. Navarrete
The expression of a functional antigen receptor is necessary for cell survival of normal B lymphocytes and most B-cell neoplasms alike. When the genetic modifications of the B-cell receptor locus fail to produce a functional antigen receptor or result in deleterious mutations of a previously expressed receptor, the affected B cell will undergo apoptosis. The three physiological mechanisms that generate the B-cell receptor, VDJ recombination, somatic hypermutation, and class switch recombination, can induce double-strand DNA breaks and can specifically contribute to lymphomagenesis. On the other hand, the B-cell receptor activation and signaling pathways, which provide strong survival and proliferation signals to normal B cells, can support the growth and evolution of malignant lymphocytes. As a result, an otherwise structurally normal B-cell receptor can behave, from the functional perspective, as a true oncogene. In this chapter, we provide an in-depth discussion of the most recently discovered recurrent mechanisms involving the B-cell receptor in lymphoma pathogenesis. The discussion is structured around two major topics: (1) the genetic mecha - nisms that create a functional antigen receptor and their errors leading to oncogenic events, and (2) the pathogenic activation of the B-cell receptor signaling cascade. Finally, we will briefly comment on novel emerging therapies targeting the B-cell receptor at different levels.
{"title":"The Antigen Receptor as a Driver of B-Cell Lymphoma Development and Evolution","authors":"J. Sepulveda, Noé Seija, P. Oppezzo, Marcelo A. Navarrete","doi":"10.5772/INTECHOPEN.72122","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.72122","url":null,"abstract":"The expression of a functional antigen receptor is necessary for cell survival of normal B lymphocytes and most B-cell neoplasms alike. When the genetic modifications of the B-cell receptor locus fail to produce a functional antigen receptor or result in deleterious mutations of a previously expressed receptor, the affected B cell will undergo apoptosis. The three physiological mechanisms that generate the B-cell receptor, VDJ recombination, somatic hypermutation, and class switch recombination, can induce double-strand DNA breaks and can specifically contribute to lymphomagenesis. On the other hand, the B-cell receptor activation and signaling pathways, which provide strong survival and proliferation signals to normal B cells, can support the growth and evolution of malignant lymphocytes. As a result, an otherwise structurally normal B-cell receptor can behave, from the functional perspective, as a true oncogene. In this chapter, we provide an in-depth discussion of the most recently discovered recurrent mechanisms involving the B-cell receptor in lymphoma pathogenesis. The discussion is structured around two major topics: (1) the genetic mecha - nisms that create a functional antigen receptor and their errors leading to oncogenic events, and (2) the pathogenic activation of the B-cell receptor signaling cascade. Finally, we will briefly comment on novel emerging therapies targeting the B-cell receptor at different levels.","PeriodicalId":114649,"journal":{"name":"Hematology - Latest Research and Clinical Advances","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123458212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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