{"product_id":"the-genetic-basis-of-haematological-cancers-isbn-9780470979389","title":"The Genetic Basis of Haematological Cancers","description":"\u003cp\u003eWritten by a team of international experts, this book provides an authoritative overview and practical guide to the molecular biology and genetic basis of haematologic cancers including leukemia. Focusing on the importance of cytogenetics and related assays, both as diagnostic tools and as a basis for translational research, this is an invaluable guide for basic and clinical researchers with an interest in medical genetics and haemato-oncology.\u003c\/p\u003e \u003cp\u003e\u003ci\u003eThe Genetic Basis of Haematological\u003c\/i\u003e \u003ci\u003eCancers\u003c\/i\u003e reviews the etiology and significance of genetic and epigenetic defects that occur in malignancies of the haematopoietic system. Some of these chromosomal and molecular aberrations are well established and already embedded in clinical management, while many others have only recently come to light as a result of advances in genomic technology and functional investigation. The book includes seven chapters written by clinical and academic leaders in the field, organised according to haematological malignancy sub-type. Each chapter includes a background on disease pathology and the genetic abnormalities most commonly associated with the condition. Authors present in-depth discussions outlining the biological significance of these lesions in pathogenesis and progression, and their use in diagnosis and monitoring response to therapy. The current or potential role of specific abnormalities as novel therapeutic targets is also discussed. There is also a full colour section containing original FISH, microarrays and immunostaining images. \u003c\/p\u003e \u003cp\u003eList of contributors xi\u003c\/p\u003e \u003cp\u003ePreface xiii\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 The myelodysplastic syndromes 1\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eCristina Mecucci, Valeria Di Battista and Valeria Nofrini\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eIntroduction 1\u003c\/p\u003e \u003cp\u003ePredisposing conditions 2\u003c\/p\u003e \u003cp\u003eFamilial platelet disorder with propensity to myeloid malignancy (FPD\/AML) 2\u003c\/p\u003e \u003cp\u003eSevere congenital neutropenia (SCN) 5\u003c\/p\u003e \u003cp\u003ePoikiloderma with neutropenia 6\u003c\/p\u003e \u003cp\u003eFamilial MDS\/AML 6\u003c\/p\u003e \u003cp\u003eShwachman–Diamond syndrome (SDS) 7\u003c\/p\u003e \u003cp\u003eDyskeratosis congenita (DKC) and telomere syndromes 8\u003c\/p\u003e \u003cp\u003eFanconi anaemia (FA) 11\u003c\/p\u003e \u003cp\u003eDown syndrome 12\u003c\/p\u003e \u003cp\u003eCytogenetics 12\u003c\/p\u003e \u003cp\u003eLoss of Y chromosome (–Y) and del(11q) 13\u003c\/p\u003e \u003cp\u003eDel(20q) 15\u003c\/p\u003e \u003cp\u003eidic(X)(q13) 15\u003c\/p\u003e \u003cp\u003eDel(17)(p13)\/i(17q) 15\u003c\/p\u003e \u003cp\u003eDel(12p) 16\u003c\/p\u003e \u003cp\u003eTrisomy 8 16\u003c\/p\u003e \u003cp\u003eRare trisomies: +6, +13, +14, +15, +16, +19, +21 16\u003c\/p\u003e \u003cp\u003eMonosomy 7 and del(7q) 17\u003c\/p\u003e \u003cp\u003eRare monosomies 19\u003c\/p\u003e \u003cp\u003eUnbalanced translocations involving 1q 19\u003c\/p\u003e \u003cp\u003et(17;18)(p10;q10) 20\u003c\/p\u003e \u003cp\u003eRare or sporadic balanced translocations 20\u003c\/p\u003e \u003cp\u003eComplex karyotypes 22\u003c\/p\u003e \u003cp\u003eChromosome 5q deletions 23\u003c\/p\u003e \u003cp\u003eSomatic mutations 31\u003c\/p\u003e \u003cp\u003eOncogenes and tumour suppressor genes 31\u003c\/p\u003e \u003cp\u003eMutations of genes involved in epigenetic modulation 39\u003c\/p\u003e \u003cp\u003eMutations of genes involved in the spliceosome machinery 45\u003c\/p\u003e \u003cp\u003eRare gene mutations in myelodysplastic syndromes 48\u003c\/p\u003e \u003cp\u003eEpigenetics 49\u003c\/p\u003e \u003cp\u003eDNA methylation 50\u003c\/p\u003e \u003cp\u003eHistone modifications 52\u003c\/p\u003e \u003cp\u003eRNA 53\u003c\/p\u003e \u003cp\u003eConclusion 54\u003c\/p\u003e \u003cp\u003eReferences 54\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Molecular genetics of the myeloproliferative neoplasms 80\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePhilip A. Beer\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eIntroduction 80\u003c\/p\u003e \u003cp\u003eOverview of the different types of mutation found in MPN patients 80\u003c\/p\u003e \u003cp\u003eAcquired mutations in cytokine signalling pathways 82\u003c\/p\u003e \u003cp\u003eAcquired mutations in pathways controlling transcriptional regulation 84\u003c\/p\u003e \u003cp\u003eAcquired mutations associated with transformation to advanced-phase disease 87\u003c\/p\u003e \u003cp\u003eInherited predisposition to clonal MPNs 87\u003c\/p\u003e \u003cp\u003eInherited non-clonal disorders that phenocopy distinct MPNs 87\u003c\/p\u003e \u003cp\u003ePolycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) 88\u003c\/p\u003e \u003cp\u003eAcquired mutations in cytokine signalling pathways (Table 2.3) 89\u003c\/p\u003e \u003cp\u003eAcquired mutations in pathways controlling transcriptional regulation (Table 2.4) 95\u003c\/p\u003e \u003cp\u003eAcquired mutations associated with progression to advanced and blastic-phase disease 101\u003c\/p\u003e \u003cp\u003eInherited predisposition to clonal MPNs 103\u003c\/p\u003e \u003cp\u003eInherited non-clonal disorders that phenocopy distinct MPNs 104\u003c\/p\u003e \u003cp\u003ePrinciples and clinical utility of laboratory testing 107\u003c\/p\u003e \u003cp\u003eChronic eosinophilic leukaemia 109\u003c\/p\u003e \u003cp\u003eAcquired mutations in cytokine signalling pathways 109\u003c\/p\u003e \u003cp\u003eAcquired mutations in pathways controlling transcriptional regulation 113\u003c\/p\u003e \u003cp\u003eAcquired mutations associated with progression to advanced and blastic-phase disease 113\u003c\/p\u003e \u003cp\u003eInherited predisposition to clonal MPNs 113\u003c\/p\u003e \u003cp\u003eInherited non-clonal disorders that phenocopy distinct MPNs 114\u003c\/p\u003e \u003cp\u003ePrinciples and clinical utility of laboratory testing 114\u003c\/p\u003e \u003cp\u003eNeoplastic mast cell disease 115\u003c\/p\u003e \u003cp\u003eAcquired mutations in cytokine signalling pathways 116\u003c\/p\u003e \u003cp\u003eAcquired mutations in pathways controlling transcriptional regulation 118\u003c\/p\u003e \u003cp\u003eAcquired mutations associated with progression to advanced and blastic-phase disease 118\u003c\/p\u003e \u003cp\u003eInherited predisposition to clonal MPNs 119\u003c\/p\u003e \u003cp\u003eInherited non-clonal disorders that phenocopy distinct MPNs 119\u003c\/p\u003e \u003cp\u003ePrinciples and clinical utility of laboratory testing 120\u003c\/p\u003e \u003cp\u003eReferences 121\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Acute myeloid leukaemia 133\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMatthew L. Smith and Thomas McKerrell\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eIntroduction 133\u003c\/p\u003e \u003cp\u003eAML classification 134\u003c\/p\u003e \u003cp\u003eCytogenetic aberrations 135\u003c\/p\u003e \u003cp\u003eFusion genes arising from structural rearrangements 135\u003c\/p\u003e \u003cp\u003eMonosomies 148\u003c\/p\u003e \u003cp\u003eComplex and monosomal karyotypes 148\u003c\/p\u003e \u003cp\u003eTrisomies 148\u003c\/p\u003e \u003cp\u003eDouble minute chromosomes 151\u003c\/p\u003e \u003cp\u003eNormal karyotype – is it really normal? 151\u003c\/p\u003e \u003cp\u003eAltered gene expression 152\u003c\/p\u003e \u003cp\u003eEVI1 152\u003c\/p\u003e \u003cp\u003eBAALC 153\u003c\/p\u003e \u003cp\u003eMN1 153\u003c\/p\u003e \u003cp\u003eERG 154\u003c\/p\u003e \u003cp\u003eSET 154\u003c\/p\u003e \u003cp\u003eBRE 154\u003c\/p\u003e \u003cp\u003eWT1 154\u003c\/p\u003e \u003cp\u003emiRNA genes 154\u003c\/p\u003e \u003cp\u003eDiagnosis and classification of AML 155\u003c\/p\u003e \u003cp\u003eCurrent risk stratification of AML patients: European LeukemiaNet (ELN) guidelines 156\u003c\/p\u003e \u003cp\u003eTherapeutic regimens in AML 158\u003c\/p\u003e \u003cp\u003eManagement of younger adults aged 18–60 years 159\u003c\/p\u003e \u003cp\u003eOlder AML patients (aged \u0026gt;60 years) 159\u003c\/p\u003e \u003cp\u003eNovel agents 160\u003c\/p\u003e \u003cp\u003eMonitoring response to therapy (MRD) 160\u003c\/p\u003e \u003cp\u003eThe genomics of AML 161\u003c\/p\u003e \u003cp\u003eClonal evolution of AML 161\u003c\/p\u003e \u003cp\u003eEstablished recurrent mutations in AML 163\u003c\/p\u003e \u003cp\u003eNovel recurrent mutations in AML 173\u003c\/p\u003e \u003cp\u003eEmerging concepts and future directions 179\u003c\/p\u003e \u003cp\u003eAge-related clonal haematopoiesis (ARCH) 179\u003c\/p\u003e \u003cp\u003eApplication of genomic technologies to the diagnosis of AML 179\u003c\/p\u003e \u003cp\u003eConclusion 181\u003c\/p\u003e \u003cp\u003eMini-glossary 183\u003c\/p\u003e \u003cp\u003eReferences 184\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Molecular genetics of paediatric acute myeloid leukaemia 203\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMarry van den Heuvel-Eibrink, Jasmijn D.E. de Rooij and Christian Michel Zwaan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eClinical introduction 203\u003c\/p\u003e \u003cp\u003eEpidemiology of AML 203\u003c\/p\u003e \u003cp\u003eDiagnostic approach 204\u003c\/p\u003e \u003cp\u003eTreatment and outcome 205\u003c\/p\u003e \u003cp\u003eRelevant molecular and genetic aberrations in paediatric AML 206\u003c\/p\u003e \u003cp\u003eType I\/II aberrations and their non-random associations 206\u003c\/p\u003e \u003cp\u003eRelevance of type I\/II aberrations for outcome and stratification of paediatric AML treatment 209\u003c\/p\u003e \u003cp\u003eEpigenetic modifiers and hydroxymethylation pathway mutations 212\u003c\/p\u003e \u003cp\u003eFurther strategies 213\u003c\/p\u003e \u003cp\u003eFurther genomic approaches to unravelling the biology of paediatric AML 213\u003c\/p\u003e \u003cp\u003eMolecularly targeted therapy 214\u003c\/p\u003e \u003cp\u003eConclusion 215\u003c\/p\u003e \u003cp\u003eReferences 215\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Acute lymphoblastic leukaemia 223\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAnna Andersson, Anthony V. Moorman, Christine J. Harrison and Charles Mullighan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eIntroduction 223\u003c\/p\u003e \u003cp\u003eChromosomal aberrations in BCP-ALL 224\u003c\/p\u003e \u003cp\u003eHigh hyperdiploidy 227\u003c\/p\u003e \u003cp\u003et(12;21)(p13;q22)\/ETV6-RUNX1 232\u003c\/p\u003e \u003cp\u003et(1;19)(q23;p13)\/TCF3-PBX1 233\u003c\/p\u003e \u003cp\u003et(17;19)(q22;p13)\/TCF3-HLF 234\u003c\/p\u003e \u003cp\u003eHypodiploidy 234\u003c\/p\u003e \u003cp\u003e11q23\/KMT2A (MLL) gene rearrangements 236\u003c\/p\u003e \u003cp\u003et(9;22)(q34;q11.1)\/BCR-ABL1 237\u003c\/p\u003e \u003cp\u003eIntrachromosomal amplification of chromosome 21 (iAMP21) 238\u003c\/p\u003e \u003cp\u003eComplex karyotype 239\u003c\/p\u003e \u003cp\u003eSubmicroscopic genetic alterations in BCP-ALL 240\u003c\/p\u003e \u003cp\u003eAlteration of transcription factors in BCP-ALL 241\u003c\/p\u003e \u003cp\u003eCRLF2 rearrangements and Janus kinase mutations in ALL 242\u003c\/p\u003e \u003cp\u003eBCR-ABL1-like or Ph-like ALL 243\u003c\/p\u003e \u003cp\u003eERG-altered ALL 245\u003c\/p\u003e \u003cp\u003eGenetic rearrangements in T-lineage ALL 245\u003c\/p\u003e \u003cp\u003eTAL1\/LMO2 rearranged T-ALL 247\u003c\/p\u003e \u003cp\u003eTLX1\/TLX3 rearranged T-ALL 248\u003c\/p\u003e \u003cp\u003eEarly T-cell precursor ALL 249\u003c\/p\u003e \u003cp\u003eOther T-ALL genetic subtypes: MLL rearranged and PICALM-MLLT10 250\u003c\/p\u003e \u003cp\u003eRelapsed ALL 251\u003c\/p\u003e \u003cp\u003eFuture directions 252\u003c\/p\u003e \u003cp\u003eReferences 252\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 The genetics of mature B-cell malignancies 265\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJonathan C. Strefford, Jude Fitzgibbon, Matthew J.J. Rose-Zerilli and Csaba Bödör\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eIntroduction 265\u003c\/p\u003e \u003cp\u003eChronic lymphocytic leukaemia 266\u003c\/p\u003e \u003cp\u003eImmunoglobulin heavy-chain variable region gene mutational status 267\u003c\/p\u003e \u003cp\u003eChromosomal banding and interphase molecular cytogenetics 268\u003c\/p\u003e \u003cp\u003eCopy number alterations 269\u003c\/p\u003e \u003cp\u003eDeletions of 13q14 269\u003c\/p\u003e \u003cp\u003eTrisomy 12 272\u003c\/p\u003e \u003cp\u003eDeletions of 11q24 and mutations of ATM 273\u003c\/p\u003e \u003cp\u003eDeletions of 17p13 and mutations of TP53 275\u003c\/p\u003e \u003cp\u003eOther copy number alterations in CLL 276\u003c\/p\u003e \u003cp\u003eGenome complexity and chromothripsis 277\u003c\/p\u003e \u003cp\u003eNovel mutations in patients with CLL 279\u003c\/p\u003e \u003cp\u003eNOTCH1 280\u003c\/p\u003e \u003cp\u003eSF3B1 281\u003c\/p\u003e \u003cp\u003eOther genes 282\u003c\/p\u003e \u003cp\u003eNovel genetic mutations in clinical practice 282\u003c\/p\u003e \u003cp\u003eGerminal centre lymphomas 284\u003c\/p\u003e \u003cp\u003eFollicular lymphoma 286\u003c\/p\u003e \u003cp\u003eDiffuse large B-cell lymphoma 293\u003c\/p\u003e \u003cp\u003eConclusions and future perspectives 296\u003c\/p\u003e \u003cp\u003eAcknowledgements 299\u003c\/p\u003e \u003cp\u003eReferences 299\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 The genetics of chronic myelogenous leukaemia 312\u003c\/b\u003e\u003cbr\u003e\u003ci\u003ePhilippa C. May, Jamshid S. Khorashad, Mary Alikian, Danilo Perrotti and Alistair G. Reid\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eIntroduction 312\u003c\/p\u003e \u003cp\u003eClinical features 313\u003c\/p\u003e \u003cp\u003eThe structure and physiological function of BCR and ABL1 316\u003c\/p\u003e \u003cp\u003eThe structure of the BCR-ABL1 fusion gene 317\u003c\/p\u003e \u003cp\u003eMechanisms of BCR-ABL1-induced oncogenesis 319\u003c\/p\u003e \u003cp\u003ePotential mechanisms underlying the genesis of CML 320\u003c\/p\u003e \u003cp\u003eCML blast crisis transformation 321\u003c\/p\u003e \u003cp\u003eTyrosine kinase inhibitor (TKI) therapy 325\u003c\/p\u003e \u003cp\u003eThe genetic basis of TKI resistance 326\u003c\/p\u003e \u003cp\u003eNovel therapeutic approaches 330\u003c\/p\u003e \u003cp\u003eGenetics in patient management 332\u003c\/p\u003e \u003cp\u003eCytogenetic and molecular cytogenetic monitoring 332\u003c\/p\u003e \u003cp\u003eQuantitative reverse transcriptase polymerase chain reaction (RT-qPCR) 334\u003c\/p\u003e \u003cp\u003eBCR-ABL1 mutation analysis 337\u003c\/p\u003e \u003cp\u003eConclusion 338\u003c\/p\u003e \u003cp\u003eReferences 339\u003c\/p\u003e \u003cp\u003eIndex 359\u003c\/p\u003e \u003cb\u003eDr Sabrina Tosi\u003c\/b\u003e graduated in Biological Sciences at the University of Milan (Italy) in 1989 and then attained her post-graduate degree in Human Cytogenetics at the University of Pavia (Italy) in 1992. Her interest in leukaemia dates back to 1989, when she started to work as a research scientist in the Department of Paediatric Haematology, Ospedale San Gerardo, Monza (Italy). In 1991-1992  Dr Tosi spent a year in the Oncogenetic Laboratory, Children's Hospital, University of Giessen (Germany) as a visiting research scientist. After another two years in Monza, Dr Tosi moved to the University of Oxford at the Weatherall Institute of Molecular Medicine, where she attained her DPhil in 1999 and spent altogether 12 years in leukaemia research. In 2005 she was appointed as Lecturer in Biosciences at Brunel University London, where she continues to work on the contribution of chromosomal abnormalities to leukaemia, with particular interest towards paediatric leukaemia.\u003cbr\u003e\u003cbr\u003e\u003cb\u003eDr Alistair Reid\u003c\/b\u003e graduated in Genetics from the University of Newcastle upon Tyne in 1995, and trained as a diagnostic genetic scientist in the UK heath service. He obtained his PhD in Cambridge in 2003 based on the characterization of novel genetic prognosticators in myeloid leukemia. Since then he has held positions at several clinical academic haematology centres including Royal Free, London and University Children’s Hospital, Zurich, and has also spent time as a consultant in the genetic diagnostics industry. In 2006 he was appointed Consultant Clinical Scientist in Molecular Pathology at Imperial College Healthcare Trust in London. He has an active laboratory-based translational research program focused on the genetics of myeloid leukemia and holds an honorary senior clinical lectureship for the development of novel methods of personalized genetic management in malignancy. Dr Reid has contributed to over 60 papers on malignancy genetics and was awarded fellowship of the Royal College of Pathologists in 2011.","brand":"Wiley-Blackwell","offers":[{"title":"Default Title","offer_id":47990239559909,"sku":"NP9780470979389","price":191.95,"currency_code":"USD","in_stock":false}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1842\/7735\/files\/9780470979389.jpg?v=1761787022","url":"https:\/\/k12savings.com\/es\/products\/the-genetic-basis-of-haematological-cancers-isbn-9780470979389","provider":"K12savings","version":"1.0","type":"link"}