IgH translocations are common in patients with primary systemic amyloidosis (al)

Suzanne R. Hayman, Richard J. Bailey, Gregory J. Ahmann, Angela Dispenzieri, Mode A. Gertz, Philip R. Greipp, Robert A. Kyle, Martha Q. Lacy, S. V. Rajkumar, Thomas E. Witzig, John A. Lust, Rafae Fonseca

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: AL is a plasma cell proliferative disorder with clinical similarities to multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), but its molecular basis is not well understood. IgH translocations are likely early genetic events in MGUS and MM and involve a large number of non-random recurrent chromosomal partners such as 1 Iql3, 4pl6.3 and 16q23. Thus we searched for evidence of IgH (14q32) translocations in 22 AL patients to determine whether these abnormalities are also present in AL. Materials and Methods: Patients were diagnosed with AL by histologie proof of amyloid deposition and evidence of a clonal plasma cell proliferation (monoclonal protein, labeling index and/or immunohistochemistry). Bone marrow specimens (plasmacytosis median 12%, range 0.5-38%), were obtained during routine clinical procurement. Plasma cells (PC) were selected with CD138 magnetic microbeads (Miltenyi Biotec) after the specimens were enriched for mononuclear cells. Cytospin preparations were subjectec to immunofluorescent detection of PC with a clone specific, AMCA-labeled, anti-light ch ain antibody. Probes that hybridize to the variable and constant regions of the IgH region were used and were directly labeled with SpectrumRed and SpectrumGreen (Vysis, Ir c), respectively. An interphase FISH break-apart strategy was employed to detect segregat ion of these probes. A normal single cell pattern consisted of 2 pairs of closely associated red and green signals, while an abnormal pattern was defined as a distance between probes of more than 3 signal-widths. A sample (100 scored PC) was considered to have an IgH translocation if the% of cells with the abnormal pattern exceeded the 99.99th percen :ile of normal cells (6.6%). Results: Ten patients (45%) showed split signals, consistent with a 14qi32 translocation, in the majority of their PC (range 39-72%). Six patients (27.3%) displayed a pattern likely compatible with an unbalanced translocation with loss of the translocated variable region probe. Two patients (9%) displayed loss of a pair of signals (range 'p77%) consistent with monosomy. The remaining 4 patients displayed non-specific abnonjial patterns. Conclusions: Our data suggest that translocations found in MM and MGUS a so occur frequently in AL. Further work is underway to identify the 14q32 partrter chromosomes for these translocations.

Original languageEnglish (US)
Pages (from-to)152a
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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