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The predominant myeloma clone at diagnosis, CDR3 defined, is constantly detectable across all stages of disease evolution

Leukemia volume 29, pages 1435–1437 (2015)Cite this article

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Multiple myeloma (MM) pathogenesis has been explained for many years by the cancer biology dogma introduced in 1976 by Peter Nowell:1 first, a single plasma cell would be immortalized by an error in the immunoglobulin genes rearrangement process; then, a progressive stepwise acquisition of somatic cell mutations would induce a sequential selection, leading to domination by the fittest clone.2 In line with this idea of ‘myeloma stability’, single-nucleotide polymorphism arrays studies in diagnostic-relapse paired samples have revealed the presence of common clonal characteristics.3 Biologically, the M-protein remains usually constant across MM evolution, to the point that it is conventionally used to monitor treatment response and disease progress. Further, the variable domain of the rearranged immunoglobulin heavy-chain genes (or CDR3 region) has been used as a patient-specific myeloma fingerprint in minimal residual disease (MRD) studies.4

However, massive genome studies with next-generation sequencing have challenged this concept in MM, showing a significant intraclonal heterogeneity at diagnosis with the possible presence of several clonal progenitors or tumor-initiating cells. Therapeutic or ecosystem-dependent selection pressures would drive the alternating dominance of these clones over time.5

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Acknowledgements

This work is partially supported by grants PS09/01450 and PI12/02311 from the Spanish ‘Instituto de Salud Carlos III (ISCIII)’, grants RD12/0036/0069 & 0058 from ‘Red Temática de Investigación Cooperativa en Cáncer (RTICC), Spanish Ministry of Economy and Competitiveness’ & European Regional Development Fund (ERDF) ‘Una manera de hacer Europa’, grant number HUS412A12-1 from the ‘Consejería de Educación de la Junta de Castilla y León’, and grant GCB-120981SAN from the ‘Asociación Española Contra el Cáncer (AECC)’. We thank Alicia Antón, Montserrat Hernández Ruano and Rebeca Maldonado for technical support.

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Authors and Affiliations

  1. Department of Hematology, University Hospital of Salamanca, Salamanca, Spain

    N Puig, I Conde, C Jiménez, M E Sarasquete, A Balanzategui, M Alcoceba, M C Chillón, E Sebastián, R Corral, L Marín, N C Gutiérrez, M-V Mateos, M González-Díaz & R García-Sanz

  2. IBSAL, Salamanca, Spain

    N Puig, I Conde, C Jiménez, M E Sarasquete, A Balanzategui, M Alcoceba, M C Chillón, E Sebastián, R Corral, L Marín, N C Gutiérrez, M-V Mateos, M González-Díaz & R García-Sanz

  3. IBMCC (USAL-CSIC), Salamanca, Spain

    N Puig, I Conde, C Jiménez, M E Sarasquete, A Balanzategui, M Alcoceba, M C Chillón, E Sebastián, R Corral, L Marín, N C Gutiérrez, M-V Mateos, M González-Díaz & R García-Sanz

  4. Department of Hematology, Hospital Miguel Servet, Zaragoza, Spain

    J Quintero

  5. Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain

    J F San-Miguel

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  1. N Puig
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Corresponding author

Correspondence to M González-Díaz.

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Puig, N., Conde, I., Jiménez, C. et al. The predominant myeloma clone at diagnosis, CDR3 defined, is constantly detectable across all stages of disease evolution. Leukemia 29, 1435–1437 (2015). https://doi.org/10.1038/leu.2015.7

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