Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients

Daniel D Billadeau, Lynn Quam, William Thomas, Neil Elliot Kay, Philip Greipp, Robert Kyle, Martin M. Oken, Brian Van Ness

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

One of the distinguishing features of multiple myeloma (MM) is the proliferation of plasma cells that home to the bone marrow (BM). However, there still remains some uncertainty concerning the presence of related malignant cells in the peripheral blood of myeloma patients. Using consensus oligonucleotide primers, we amplified the third complementary determining region (CDR3) of rearranged immunoglobulin heavy chain alleles from MM marrow samples by polymerase chain reaction (PCR). From the sequences of the products, we derived allele-specific oligonucleotides (ASO), and these were used in subsequent amplification reactions to detect malignant clones in the peripheral blood of myeloma patients. This method is highly specific and sensitive to 1 malignant cell in the background of 105 normal cells. Using this method we detected circulating malignant cells in 13 of 14 previously untreated MM patients. Furthermore, by applying ASO-PCR to artificial titrations of initial BM DNA sample into normal peripheral blood lymphocyte (PBL) DNA we were able to generate standard curves and quantitate the amount of tumor in the patient PBL. We observed a wide variation in the amount of circulating tumor between patients. In addition, we found that the incidence of circulating tumor cells was independent of BM tumor burden and stage of disease. The detection and quantitation of circulating tumor cells in the PBL of MM patients may offer an alternative assessment of the disease and may be an important consideration in the use of peripheral stem cells in bone marrow transplantation.

Original languageEnglish (US)
Pages (from-to)1818-1824
Number of pages7
JournalBlood
Volume80
Issue number7
StatePublished - Oct 1 1992

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Multiple Myeloma
Tumors
Blood
Lymphocytes
Bone
Bone Marrow
Polymerase chain reaction
Circulating Neoplastic Cells
Alleles
Cells
Immunoglobulin Heavy Chains
DNA Primers
DNA
Polymerase Chain Reaction
Stem cells
Titration
Oligonucleotides
Amplification
Plasma Cells
Tumor Burden

ASJC Scopus subject areas

  • Hematology

Cite this

Billadeau, D. D., Quam, L., Thomas, W., Kay, N. E., Greipp, P., Kyle, R., ... Van Ness, B. (1992). Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. Blood, 80(7), 1818-1824.

Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. / Billadeau, Daniel D; Quam, Lynn; Thomas, William; Kay, Neil Elliot; Greipp, Philip; Kyle, Robert; Oken, Martin M.; Van Ness, Brian.

In: Blood, Vol. 80, No. 7, 01.10.1992, p. 1818-1824.

Research output: Contribution to journalArticle

Billadeau, DD, Quam, L, Thomas, W, Kay, NE, Greipp, P, Kyle, R, Oken, MM & Van Ness, B 1992, 'Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients', Blood, vol. 80, no. 7, pp. 1818-1824.
Billadeau, Daniel D ; Quam, Lynn ; Thomas, William ; Kay, Neil Elliot ; Greipp, Philip ; Kyle, Robert ; Oken, Martin M. ; Van Ness, Brian. / Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. In: Blood. 1992 ; Vol. 80, No. 7. pp. 1818-1824.
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