Multiple Myeloma


Multiple myeloma is a clonal bone marrow disease characterized by the neoplastic transformation of terminally differentiated B cells that secrete a homogeneous (monoclonal) immunoglobin called an M-protein or paraprotein. Multiple myeloma is characterized by excess bone marrow plasma cells, monoclonal proteins, osteolytic bone lesions, renal impairment, anemia, and immunodeficiency.

Myeloma can progress through stages that in some cases may include a pre-malignant monoclonal expansion of plasma cells called monoclonal gammopathy of undetermined significance (MGUS) which is characterized by <10% plasma cells in the bone marrow, monoclonal protein spike, and no end organ damage. It may also include smoldering myeloma or asymptomatic myeloma which shows 10-30% plasma cells in the bone marrow but no osteolytic lesions, anemia or other features of malignant myeloma.


Multiple Myeloma mutation detection is offered for patients with plasma cells >10% in a bone marrow aspirate or with a diagnosis of multiple myeloma with less <10% clonal plasma cells in the BM.


  • Completed CGL Lymphoid Testing or CGL Myeloid Testing requisition form
  • One of the following specimens (please see our Specimen Guidelines, Cytogenetics FISH test type):
    • 4mL peripheral blood collected in sodium heparin tubes (green top)
    • 2×1.0 mL of marrow aspirate in 9mL media (RPMI 1640, 3.8% FBS, antibiotics)
  • Also accepted, but not preferred specimens include:
    • Bone marrow biopsy in 9mL media (RPMI 1640, 3.8% FBS, antibiotics)
  • NOTE: Plasma cell isolation is performed on the specimen prior to testing. If additional tests are requested, a second specimen is required. Please see our guidelines for multiple test ordering.


Results are reported within fourteen days from receipt of a Bone Marrow report indicating greater than 10% clonal plasma cells.  Specimen received in CGL for the indication of Multiple Myeloma will be processed and suspended pending a BM report.


The plasma cell enriched pellet is used to perform FISH analysis using the following probes:

  • dual-colour probe to CKS1B/CDKN2C (Cytocell)
  • dual-colour break-apart probe to IGH (Cytocell)
  • TP53 and CEP17 probe (Cytocell)

Deletions of TP53 occur in ~8% of MM cases and are associated with a poor prognosis.

Gains (>2 copies) of the 1q21 region (CKS1B) and deletions of the 1p32 region (CDKN2C) are both associated with poor prognosis.

If the specimen is positive for an IGH rearrangement, reflex FISH analysis will be performed using the following probes dual-colour, dual-fusion translocation probes:

  • IGH-FGFR3 (Vysis)
  • IGH-MAF (Vysis)
  • IGH-CCND1 (Vysis)

Rearrangements involving IGH and a variety of partner genes are present in up to 70% of MM. Rearrangements with CCND1 occur in ~16% of cases and are associated with a favourable prognosis. Rearrangements with FGFR3 and MAF occur in ~15% and ~5% of cases respectively, and are both associated with a poor prognosis.

If the specimen is negative for an IGH rearrangement, FISH using the above dual colour, dual fusion probes will not be performed.


Plasma cell isolation is performed using a CD138 selection on one of the two submitted BM media tubes.  The second tube is set up for overnight culture in the event of a change in diagnosis requiring a karyotype.

The following FISH probes are used in this panel.


  1. Du et al. Leuk Lymphoma (2020) PMID: 31842644
  2. NCCN Guidelines – Multiple myeloma v.2021