Advancement of Multiple Myeloma From Diagnosis Through Plateau Phase to Progression Does Not Involve a New B-Cell Clone: Evidence From the Ig Heavy Chain Gene

The Ig heavy chain (IgH) gene was used as a marker to investigate clonal succession and the origin of the neoplastic cell in multiple myeloma. The polymerase chain reaction (PCR) was used to amplify a section of the rearranged IgH gene at diagnosis and at progression in 21 patients who had exhibited...

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Published inBlood Vol. 82; no. 1; pp. 202 - 206
Main Authors Ralph, Quentin M., Brisco, Michael J., Joshua, Doug E., Brown, Ross, Gibson, John, Morley, Alexander A.
Format Journal Article
LanguageEnglish
Published Washington, DC Elsevier Inc 01.07.1993
The Americain Society of Hematology
Subjects
B-Lymphocytes - cytology
Base Sequence
Biological and medical sciences
Clone Cells
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Genes, Immunoglobulin
Hematologic and hematopoietic diseases
Humans
Immunoglobulin Heavy Chains - genetics
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Molecular Sequence Data
Multiple Myeloma - genetics
Multiple Myeloma - pathology
Oligodeoxyribonucleotides - chemistry
Polymerase Chain Reaction
Human
Immunoglobulins
Malignant hemopathy
Diagnosis
Myeloma
heavy-Peptide chain
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Summary:The Ig heavy chain (IgH) gene was used as a marker to investigate clonal succession and the origin of the neoplastic cell in multiple myeloma. The polymerase chain reaction (PCR) was used to amplify a section of the rearranged IgH gene at diagnosis and at progression in 21 patients who had exhibited a plateau phase. A monoclonal PCR product was seen for 16 of the patients and the product present at progression was of the same molecular weight as that at diagnosis. This finding suggests that the IgH rearrangement present at diagnosis and progression was the same. This was confirmed by sequencing the IgH gene in 10 patients. The IgH genes were found to be hypermutated at diagnosis, but no further hypermutation occurred during the course of the disease. The results provide evidence that the neoplastic cell in myeloma may originate as a memory B cell, plasmablast, or plasma cell, and suggest that progression beyond the plateau phase is not caused by clonal succession.
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ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V82.1.202.bloodjournal821202