Brief Report haematologica | 2010; 95(7) 1221 A large series of plasma cell dyscrasias (n=2207) was exam- ined for translocations which deregulate the MAF genes, t(14;20)(q32;q12) and t(14;16)(q32;q23), and their disease behavior was compared to a group characterized by the t(4;14)(p16;q32) where CCND2 is also up-regulated. The t(14;20) showed low prevalence in myeloma (27/1830, 1.5%) and smoldering myeloma (1/148, <1%) with a higher inci- dence in MGUS (9/193, 5% P=0.005). Strong associations with del(13) (76%), non-hyperdiploidy (83%) and gain of 1q (58%) were seen but no association with an IgA M-protein or absence of bone disease was noted. All three transloca- tions were associated with poor outcome in myeloma, but strikingly all t(14;20) MGUS/smoldering myeloma cases (n=10) had stable, low level disease. In contrast, the 10 t(14;16) and 25 t(4;14) MGUS/smoldering myeloma cases were associated with both evolving and non-evolving dis- ease. None of the associated genetic abnormalities helped to predict for progression from MGUS or smoldering myeloma. (Clinicaltrials.gov identifier: ISRCTN 68454111; UKCRN ID 1176) Key words: plasma cell, myeloma, MGUS, chromosome abnormality, disease progression. Citation: Ross FM, Chiecchio L, Dagrada G, Protheroe RKM, Stockley DM, Harrison CJ, Cross NCP, Szubert AJ, Drayson MT, Morgan GJ on behalf of the UK Myeloma Forum.The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease in monoclonal gammopathies of undetermined significance. Haematologica 2010;95:1221-1225. doi:10.3324/haematol.2009.016329 ©2010 Ferrata Storti Foundation. This is an open-access paper. Introduction Approximately half of myeloma (MM) cases are character- ized by translocations into the immunoglobulin heavy chain locus (IgH). Each translocation subgroup is associated with deregulation of a D group cyclin either directly, such as occurs with the t(11;14) (cyclin D1) and t(6;14) (cyclin D3) or indi- rectly, such as occurs with the t(4;14) or in the MAF translo- cation group. 1 The MAF translocation group includes the t(14;16) and t(14;20), both of which are rare in myeloma, but are thought to be associated with poor prognosis. 2 The mechanism of this poor outcome is thought to involve the consequences of MAF upregulation, which include upregula- tion of cyclin D2, effects on cell interaction and upregulation of apoptosis resistance. 3 As upregulation of cyclin D2 is also seen in the t(4;14) group where poor prognosis is well estab- lished, 4-8 it may be deregulation of this D group cyclin which is important in this respect. MM cases with t(4;14) show an excess of IgA M-protein type 9 and have been reported to be less likely to present with bone disease (1) but it is not clear whether this also applies to the other cyclin D2 dysregulating translocations, t(14;16) and t(14;20) cases. MGUS is a benign premylomatous condition lacking the clinical sequelae of myeloma, but with a rate of transforma- tion to myeloma of approximately 1% per year. 10 This rela- tionship has led to the generation of disease models of myeloma based on the multistep progression of normal to MGUS through to myelomatous plasma cells. 11 In these mod- els, initial genetic hits result in an immortalized plasma cell clone and additional changes lead to its transformation to clinical myeloma. With the recent recognition that essential- ly all myeloma cases have a pre-existing asymptomatic phase, 12-13 it becomes even more important to recognize which abnormalities affect the rate of progression. The t(4;14) has been reported to be rare in MGUS and smoldering/asymptomatic MM (SMM), leading to the sug- gestion that it is associated with an aggressive disease process effectively bypassing this stage. 9,14 However, there are reports The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease in monoclonal gammopathies of undetermined significance Fiona M. Ross, 1 Laura Chiecchio, 1 GianPaolo Dagrada, 1 Rebecca K.M. Protheroe, 1 David M. Stockley, 1 Christine J. Harrison, 2 Nicholas C.P. Cross, 1 Alex J. Szubert, 3 Mark T. Drayson, 4 Gareth J. Morgan 5 on behalf of the UK Myeloma Forum 1 LRF UKMF Cytogenetic Database, University of Southampton, Wessex Regional Genetics Laboratory, Salisbury, Wilts; 2 Northern Institute of Cancer Research, Newcastle University, Newcastle; 3 Clinical Trials Research Unit, University of Leeds, Leeds, and 4 Division of Immunity and Infection, University of Birmingham, and 5 the Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK ABSTRACT Acknowledgments: we thank Leukaemia Research for funding this work, Catherine Stacey-Richardson and the referring clinicians and their research nurs- es who have provided clinical details, and Faith Davies, Sue Bell and Walter Gregory for various aspects of the Myeloma IX trial. Funding: this work was funded by Leukaemia Research. Manuscript received on August 27, 2009. Revised version arrived on December 18, 2009. Manuscript accepted on January 7, 2010. Correspondence: Fiona Ross, Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts, SP2 8BJ, UK. E-mail: fiona.ross@salisbury.nhs.uk