Translocation (11;14) is a common cytogenetic abnormality in clonal plasma cells in monoclonal immunoglobulin deposition disease

Br J Haematol. 2024 Nov;205(5):1860-1865. doi: 10.1111/bjh.19748. Epub 2024 Sep 6.

Abstract

Monoclonal Immunoglobulin deposition disease (MIDD) is characterised by deposits of intact monoclonal light chains in the kidney leading to renal dysfunction. In this study, we retrospectively investigated the underlying plasma cell cytogenetic abnormalities in MIDD. CyclinD1 (11;14) translocation was identified in 12/27 (45%) patients. Among the patients without translocation, del13q and hyperdiploidy were the most common abnormalities. Patients in the non-t (11;14) group had a higher baseline light-chain ratio, higher proteinuria and lower eGFR as compared to patients with t (11;14). Haematological VGPR or higher was seen in 58% of t (11;14), and 30% without t (11;14), possibly related to higher use of Daratumumab-based therapy in the t (11;14) group. With a median follow-up of 750 days, 30% (8/24) progressed to end stage renal disease (ESRD). eGFR <20 mL/min (HR 25, 95% CI 2.09-298, p = 0.01) and 24 urine protein >3 g/24 h (HR 9, 95% CI 1.27-63.90, p = 0.02) at diagnosis were significantly associated with progression to ESRD. Renal survival was better in t (11;14) as compared to the non-t (11;14) group (HR 0.11, p = 0.06). Translocation (11;14) is a common abnormality in MIDD and affects the presentation and outcomes. Identification of this abnormality should lead to exploration of BCL2 inhibitors in this disease.

Keywords: cytogenetics; light chain deposition disease; monoclonal immunoglobulin deposition disease.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 14* / genetics
  • Cyclin D1 / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paraproteinemias / genetics
  • Paraproteinemias / pathology
  • Plasma Cells* / metabolism
  • Plasma Cells* / pathology
  • Retrospective Studies
  • Translocation, Genetic*

Substances

  • Antibodies, Monoclonal
  • Cyclin D1