title: Myeloma Propagating Cells, Drug Resistance and Relapse.
abstract: Multiple myeloma (MM) is an incurable tumor of the plasma cells, the terminally differentiated immunoglobulin secreting B lineage cells. The genetic make-up of MM has been extensively characterized but its impact on the biology of the disease is incomplete without more precise knowledge of the identity and functional role of cells with multiple myeloma propagating activity (MMPA). We review here recent data that link MMPA with myeloma clonotypic populations organized in a cellular hierarchy that mirrors normal B cell development and also with drug resistance and disease relapse. We further propose a conceptual framework which, with optimal use of recent technological advances in genomics and phenomics, could allow dissection of the cellular and molecular properties of cells with MMPA, drug resistance and in vivo relapse in an integrated and patient-specific manner. There is real hope that these approaches will significantly contribute to further improvements in disease control, overall survival, and possibly cure of patients with MM.
authors: Centre for Haematology, Department of Medicine, Imperial College London, London, United Kingdom.|Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors: Anastasios
authors: A
authors: Karadimitris
authors: Centre for Haematology, Department of Medicine, Imperial College London, London, United Kingdom.|Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors: Aristeidis
authors: A
authors: Chaidos
authors: Centre for Haematology, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Valentina
authors: V
authors: Caputo
authors: Centre for Haematology, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Katerina
authors: K
authors: Goudevenou
authors: Centre for Haematology, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Kanagaraju
authors: K
authors: Ponnusamy
authors: Centre for Haematology, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Xiaolin
authors: X
authors: Xiao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents
keywords: B lymphocytes; Cancer; Cancer stem cells; Epigenetics; Flow cytometry; Hematologic malignancies; Stem cell plasticity; Xenotransplantation