Chapters authored
Genomics of Acute Myeloid Leukemia
Acute myelogenous leukemia (AML) is a clonal, malignant disease of hematopoietic tissue that is characterized by accumulation of abnormal (leukemic) blast cells, principally in the bone marrow. Representation of these genetic mutations and the involvement patterns seems to follow specific and temporally ordered fluctuating manners. Somatic mutations in these genes are represented as a variety of recurrent chromosomal abnormalities, e.g., t (8;21), t(15;17), etc., or by the presence of prognostic markers, e.g., FLT3, MLL, NPM1 and CEBPA as well as encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. The same genes are frequently found to be mutated in elderly individuals along with clonal expansion of hematopoiesis that confers an increased risk for the development of hematologic cancers. Furthermore, such genomic changes may persist after therapy, lead to clonal expansion during hematologic remission, and eventually lead to relapsed disease. Majority of genetic data are now being used to classification, risk stratification, and clinical care of patients. The unprecedented molecular characterization provided by advanced and deeply sensitized molecular assays like next-generation sequencing (NGS) offers the potential for an individualized approach to treatment in AML, bringing us one step closer to personalized medicine.
Part of the book: Myeloid Leukemia
Therapeutic Targets and Signaling Pathways for Diagnosis of Myeloma
Multiple myeloma (MM) is a malignancy of plasma cells that not only shows different clinical behavior but also depicts heterogeneous groups at molecular level. The prognosis of the disease has been dramatically changed with the arrival of new drugs in the past few years. In this context of better therapeutic agents, there are important challenges for accurate evaluation of patients by better prognostic and predictive tools. Transcriptomic studies have largely added to decipher MM heterogeneity, dividing MM patients into different subgroups according to prognosis. Micro-arrays and more recently RNA sequencing have helped in evaluating coding and non-coding genes, mutations, unique transcriptome convertors and different splicing events giving new information concerning biology, outcome and treatment options. Initial data from gene expression profiling studies have also pointed out genes that predict prognosis, i.e., CSK1-B, and can deliver pharmacogenomics and biologic vision into the pathophysiology, targeted treatment, and future direction. Importantly, we suggest that all prospective studies and clinical trials now accept genetic testing and risk stratification of MM patients. In this review, we discuss the part and effect of gene expression profiling in myeloma.
Part of the book: Update on Multiple Myeloma