Targeting plasma cells improves detection of cytogenetic aberrations in multiple myeloma: phenotype/genotype fluorescence in situ hybridization

Cancer Genet Cytogenet. 2005 Apr 15;158(2):99-109. doi: 10.1016/j.cancergencyto.2005.01.006.


Standard fluorescence in situ hybridization (FISH) easily detects nonrandom karyotypic abnormalities in multiple myeloma (MM) at disease presentation, when tumor burden is high. In contrast, the detection of residual MM using the standard 200 unselected nonmitotic nuclei FISH approach correlates poorly with residual disease detected by morphology, flow cytometry, immunohistochemistry, or reverse-transcription polymerase chain reaction (RT-PCR). We have used sequential May-Grunwald Giemsa stain to identify plasma cell populations, followed by FISH analyses (target FISH or T-FISH) to detect immunoglobulin heavy-chain gene (IGH) rearrangements, 13q or 17p deletions, or hyperdiploidy. In this study, 115 samples were collected from 100 patients with MM regardless of treatment status. In this proof-of-principle prospective study, T-FISH detected MM in 52 samples (45%), a percentage similar to that obtained by pathology. Disease detection increased from 5.6% with standard FISH to 48% with T-FISH, and cell culture experiments showed that T-FISH consistently detected a clonal abnormality at dilutions of 10(-3). In five patients, T-FISH further identified myelodysplastic-associated karyotypic changes restricted to myeloid cells. Our observations suggest that T-FISH identifies cell lineage involvement of cytogenetic abnormalities, improves detection of low-level or residual MM, and may define the coexistence of hematologic karyotypic changes in individual patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Lineage
  • Cells, Cultured
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 13
  • Chromosomes, Human, Pair 17
  • Clone Cells / pathology
  • Cytogenetic Analysis
  • Eosine Yellowish-(YS)
  • Female
  • Genotype*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • In Situ Hybridization, Fluorescence*
  • Male
  • Methylene Blue
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics*
  • Phenotype*
  • Plasma Cells / pathology*
  • Ploidies
  • Prospective Studies
  • Sensitivity and Specificity


  • Immunoglobulin Heavy Chains
  • May-Grunwald Giemsa
  • Methylene Blue
  • Eosine Yellowish-(YS)