Co-existent hyperdiploidy does not abrogate poor prognosis in myeloma with adverse cytogenetics and may precede IGH-translocations

Pawlyn, C., Melchor, L., Murison, A., Wardell, C.P., Brioli, A., Boyle, E.M., Kaiser, M.F., Walker, B.A., Begum, D.B., Dahir, N.B., Proszek, P., Gregory, W.M., Drayson, M.T., Jackson, G.H., Ross, F.M., Davies, F.E. and Morgan, G.J. (2015) Co-existent hyperdiploidy does not abrogate poor prognosis in myeloma with adverse cytogenetics and may precede IGH-translocations. Blood, 125 (5), 831-840. (doi:10.1182/blood-2014-07-584268). (PMID:25428216)

Abstract

The acquisition of the cytogenetic abnormalities hyperdiploidy or translocations into the immunoglobulin gene loci are considered as initiating events in the pathogenesis of myeloma and were often assumed to be mutually exclusive. These lesions have clinical significance with hyperdiploidy or the presence of the t(11;14) translocation associated with a favorable outcome whilst t(4;14), t(14;16) and t(14;20) are unfavorable. Poor outcomes are magnified when lesions occur in association with other high-risk features, del17p and +1q. Some patients have co-existence of both good and poor prognostic lesions and there has been no consensus on their risk status. To address this we have investigated their clinical impact using cases in the Myeloma IX study (ISRCTN68454111) and shown that the co-existence of hyperdiploidy or t(11;14) does not abrogate the poor prognosis associated with adverse molecular lesions, including translocations. We have also used single cell analysis to study cases with co-existent translocations and hyperdiploidy, to determine how these lesions co-segregate within the clonal substructure, and demonstrated that hyperdiploidy may precede IGH translocation in a proportion of patients. These findings have important clinical and biological implications as we conclude patients with coexistence of adverse lesions and hyperdiploidy should be considered high-risk and treated accordingly.

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