Cytogenetic intraclonal heterogeneity of plasma cell dyscrasia in AL amyloidosis as compared with multiple myeloma

Tilmann Bochtler, Maximilian Merz, Thomas Hielscher, Martin Granzow, Korbinian Hoffmann, Alwin Krämer, Marc-Steffen Raab, Jens Hillengass, Anja Seckinger, Christoph Kimmich, Tobias Dittrich, Carsten Müller-Tidow, Dirk Hose, Hartmut Goldschmidt, Ute Hegenbart, Anna Jauch, Stefan O Schönland

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Analysis of intraclonal heterogeneity has yielded insights into the clonal evolution of hematologic malignancies. We compared the clonal and subclonal compositions of the underlying plasma cell dyscrasia in 544 systemic light chain amyloidosis (PC-AL) patients with 519 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or symptomatic MM; ie, PC-non-AL patients). Using interphase fluorescence in situ hybridization, subclones were stringently defined as clone size below two thirds of the largest clone and an absolute difference of ≥30%. Subclones were found less frequently in the PC-AL group, at 199 (36.6%) of 544 as compared with 267 (51.4%) of 519 in the PC-non-AL group (P < .001), and were not associated with the stage of plasma cell dyscrasia in either entity. In both groups, translocation t(11;14), other immunoglobulin heavy chain translocations, and hyperdiploidy were typically found as main clones, whereas gain of 1q21 and deletions of 8p21, 13q14, and 17p13 were frequently found as subclones. There were no shifts in the subclone/main clone ratio depending on the MGUS, SMM, or MM stage of plasma cell dyscrasia. In multivariate analysis, t(11;14) was associated with lower rates of subclone formation and hyperdiploidy with higher rates. PC-AL itself lost statistical significance, demonstrating that the lower subclone frequency in AL is a reflection of its exceptionally high t(11;14) frequency. In summary, the subclone patterns in PC-AL and PC-non-AL are closely related, implying that subclone formation depends on the main cytogenetic categories and is independent of disease entity and stage.

Original languageEnglish
Pages (from-to)2607-2618
Number of pages12
JournalBlood Advances
Volume2
Issue number20
DOIs
Publication statusPublished - 23 Oct 2018

Bibliographical note

© 2018 by The American Society of Hematology.

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytogenetics/methods
  • Female
  • Humans
  • Immunoglobulin Light-chain Amyloidosis/genetics
  • Male
  • Middle Aged
  • Multiple Myeloma/genetics
  • Paraproteinemias/genetics

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