P Leif Bergsagel

Introduction, 115

Stages of multiple myeloma, 115

Multiple myeloma is a plasma cell tumor with frequent Ig translocations, 116

Marked karyotypic instability, 116

Recurrent chromosomal partners for Ig translocations: 11q13, 6p21, 4p16, 16q23 and 20q11, 116

Secondary translocations dysregulate MYC, 116

Dysregulation of cyclin D1, 2 or 3: a unifying oncogenic event in multiple myeloma, 117

A model for the molecular pathogenesis of multiple myeloma, 117

Proposal for a six-group translocation/cyclin D classification of multiple myeloma tumors, 118

The translocation/cyclin D molecular classification predicts prognosis and response to therapies, 119 A tumor suppressor gene on chromosome 13?, 119 Activating Ras and FGFR3 mutations, 120 Identification of novel therapeutic strategies targeting genetic abnormalities, 120 Critical but variable role for the bone marrow microenvironment, 121 Therapies that target the multiple myeloma cell and the microenvironment, 121

Conclusions, 121 Further reading, 122

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