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The Molecular Pathogenesis of Multiple Myeloma

Niccolò Bolli
Giovanni Martinelli
3 and
Claudio Cerchione
Department of Oncology and Hemato-Oncology, University of Milan, 20133 Milan, Italy
Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20133 Milan, Italy
Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014 Meldola, Italy
Author to whom correspondence should be addressed.
Hematol. Rep. 2020, 12(3), 9054;
Submission received: 14 December 2020 / Revised: 15 December 2020 / Accepted: 15 December 2020 / Published: 18 December 2020


Multiple Myeloma (MM) is characterized by uncontrolled proliferation and accumulation of clonal plasma cells within the bone marrow. However, the cell of origin is a B-lymphocyte acquiring aberrant genomic events in the germinal center of a lymph node as off-target events during somatichypermutation and class-switch recombination driven by activation-induced-deaminase. Whether pre-germinal center events are also required for transformation, and which additional events are required for disease progression is still matter of debate. As early treatment in asymptomatic phases is gaining traction in the clinic, a better understanding of the molecular pathogenesis of myeloma progression would allow stratification of patients based on their risk of progression, thus rationalizing efficacy and cost of clinical interventions. In this review, we will discuss the development of MM, from the cell of origin through asymptomatic stages such as monoclonal gammopathy of undetermined significance and smoldering MM, to the development of symptomatic disease. We will explain the genetic heterogeneity of MM, one of the major drivers of disease recurrence. In this context, moreover, we will propose how this knowledge may influence future diagnostic and therapeutic interventions.
Keywords: multiple myeloma; tumor evolution; next-generation sequencing; personalized medicine multiple myeloma; tumor evolution; next-generation sequencing; personalized medicine

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MDPI and ACS Style

Bolli, N.; Martinelli, G.; Cerchione, C. The Molecular Pathogenesis of Multiple Myeloma. Hematol. Rep. 2020, 12, 9054.

AMA Style

Bolli N, Martinelli G, Cerchione C. The Molecular Pathogenesis of Multiple Myeloma. Hematology Reports. 2020; 12(3):9054.

Chicago/Turabian Style

Bolli, Niccolò, Giovanni Martinelli, and Claudio Cerchione. 2020. "The Molecular Pathogenesis of Multiple Myeloma" Hematology Reports 12, no. 3: 9054.

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