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VH gene usage is multiple myeloma: complete absence of the VH4.21 (VH4- 34)
gene
MB Rettig, RA Vescio, J Cao, CH Wu, JC Lee, E Han, M DerDanielian, R Newman, C Hong, AK Lichtenstein and JR Berenson
Department of Medicine, DVA West Los Angeles, UCLA School of Medicine, CA
90073, USA.
The immunoglobin heavy chain variable region (VH) gene usage in multiple
myeloma (MM) has not been reported, although a few studies have
incidentally identified the VH gene rearranged in small cohorts of MM
patients. We used a reverse transcriptase-polymerase chain reaction based
technique to analyze the VH gene usage in MM. The VH sequences were
obtained after amplification of bone marrow cDNA using the seven VH
family-specific and constant region primers. The VH sequences of 72
patients were successfully identified. The frequency of VH family usage in
decreasing order was VH3>VH4>VH1>VH5>VH2>VH6>VH7 and
corresponded to the functional germline complexity of the VH families.
Individual VH genes (VH1-69, VH3-9, VH3-23, and VH3-30) were
overrepresented in our cohort of MM patients; some VH genes [VH3-49,
VH3-53, and VH4.21 (VH4- 34)], which are rearranged with increased
frequency in normal circulating B cells, autoimmune diseases, and other
B-cell malignancies, were not detected in any MM patient. Compared with
germline sequences, an average of 8.8% (range, 2.7% to 16.5%) of the
nucleotides had evidence of mutation within each VH sequence. Based on
these results, we conclude that (1) the VH gene usage in MM is unique
compared with other malignant and nonmalignant B-cell populations, (2) the
physiologic process of clonal deletion functions to remove clones that have
rearranged VH genes (VH4.21) capable of expressing antibodies, which
recognize self-antigens, and (3) the complete lack of VH4.21 gene
rearrangement may help to partially explain the paucity of autoimmune
phenomena in MM.
Volume 87,
Issue 7,
pp. 2846-2852,
04/01/1996
Copyright © 1996 by The American Society of Hematology
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