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Myeloma

Genetic aberrations and survival in plasma cell leukemia

Leukemia volume 22, pages 1044–1052 (2008)Cite this article

Abstract

Plasma cell leukemia (PCL) is an aggressive and rare hematological malignancy that originates either as primary disease (pPCL) or as a secondary leukemic transformation (sPCL) of multiple myeloma (MM). We report here the genetic aberrations and survival of 80 patients with pPCL or sPCL and make comparisons with 439 cases of MM. pPCL presents a decade earlier than sPCL (54.7 vs 65.3 years) and is associated with longer median overall survival (11.1 vs 1.3 months; P<0.001). 14q32 (IgH) translocations are highly prevalent in both sPCL and pPCL (82–87%); in pPCL IgH translocations almost exclusively involve 11q13 (CCND1), supporting a central etiological role, while in sPCL multiple partner oncogenes are involved, including 11q13, 4p16 (FGFR3/MMSET) and 16q23 (MAF), recapitulating MM. Both show ubiquitous inactivation of TP53 (pPCL 56%; sPCL 83%) by coding mutation or 17p13 deletion; complemented by p14ARF epigenetic silencing in sPCL (29%). Both show frequent N-RAS or K-RAS mutation. Poor survival in pPCL was predicted by MYC translocation (P=0.006). Survival in sPCL was consistently short. Overall pPCL and sPCL are different disorders with distinct natural histories, genetics and survival.

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Acknowledgements

This work was supported in part by the Donaldson Charitable fund Trust, Public Health Service grant no. R01 CA83724-01 (RF) and P01 CA62242 (RF, AD, RAK, PRG) from the National Cancer Institute. RF and PRG are supported by the CI-5 Cancer Research Fund-Lilly Clinical Investigator Award of the Damon Runyon Cancer Research Fund. PRG and RF are also supported by the ECOG Grant CA21115-25C from the National Cancer Institute. RET is supported by a fellowship from AMGEN and the Haematology Society of Australia and New Zealand (HSANZ).

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Author notes

  1. R E Tiedemann and N Gonzalez-Paz: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA

    R E Tiedemann, S A Van Wier, W J Chng, P L Bergsagel, A K Stewart & R Fonseca

  2. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    N Gonzalez-Paz, R A Kyle, T Price-Troska, M A Gertz, K Henderson, P R Greipp, A Dispenzieri, M Q Lacy & S V Rajkumar

  3. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    R Santana-Davila

  4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    R P Ketterling

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Correspondence to R Fonseca.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Tiedemann, R., Gonzalez-Paz, N., Kyle, R. et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 22, 1044–1052 (2008). https://doi.org/10.1038/leu.2008.4

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