Uthe Clinical and Biological Consequences of Different Flt3 Mutations in Patients with Aml

..................................................................................................................... 3 ACKNOWLEDGEMENTS .............................................................................................. 4 TABLE OF CONTENTS.................................................................................................. 5 LIST OF FIGURES ........................................................................................................ 12 LIST OF TABLES .......................................................................................................... 15 COMMONLY USED ABBREVIATIONS .................................................................... 17 CHAPTER 1: INTRODUCTION ................................................................................... 18 1.1 Clinical presentation of AML ......................................................................... 18 1.2 Diagnosis and classification of AML.............................................................. 19 1.2.1 French American British (FAB) classification .......................................19 1.2.2 Secondary and therapy related AML ......................................................19 1.2.3 Recurrent cytogenetic abnormalities in AML.........................................19 1.2.4 World health organisation (WHO) classification....................................20 1.3 Prognostic factors in patients with AML ........................................................ 20 1.3.1 Clinical Prognostic Factors .....................................................................23 1.3.2 Cytogenetic Risk Groups ........................................................................23 1.3.3 Combining different prognostic factors ..................................................24 1.3.4 Molecular Prognostic Factors .................................................................25 1.4 Conventional Chemotherapeutic Approaches in AML................................... 26 1.4.1 Induction Chemotherapy for non-APL AML .........................................26 1.4.2 Consolidation Chemotherapy..................................................................27 1.4.3 Autologous stem cell transplantation (SCT) ...........................................27 1.4.4 Allogeneic SCT.......................................................................................27 1.4.5 Acute Promyelocytic Leukaemia (APL).................................................28 1.5 Risk-adapted therapy....................................................................................... 28 1.5.1 Monitoring for minimal residual disease (MRD)....................................29 1.6 Molecular and cellular pathogenesis of AML................................................. 29 1.6.1 Oncogenes ...............................................................................................30 1.6.2 Mutations in growth factor receptors in AML ........................................31 1.6.3 Cooperating genetic events in leukaemogenesis.....................................32