Cross-lineage gene rearrangements in human leukemic B-precursor cells occur
frequently with V-DJ rearrangements of IgH genes
T Nosaka, K Kita, H Miwa, K Kawakami, T Ikeda, T Ohno, N Matsuoka, Y Arita, S Doi and M Nishikori
Institute for Virus Research, Kyoto University, Japan.
Gene configurations of immunoglobulin (Ig), T-cell antigen receptor (TCR)
beta chain, and T-cell rearranging gene gamma (TRG gamma) were studied in
human B-precursor lymphoblastic leukemic cells. These cells were
phenotypically classified into three developmental stages (stages II
through IV) according to Nadler's criteria. All of them showed the Ig heavy
chain (IgH) gene rearrangement, and 67% of the cells in stage IV had the
rearranged TRG gamma, albeit seldom in other stages. We further analyzed
IgH gene rearrangements in detail using upstream to DH (diversity region of
IgH) region probe to distinguish DJ from V-DJ recombination. All dual
genotyped cells in each stage except one case in stage II showed the V-DJ
rearrangements. This suggests the cross- lineage involvement of the
putative recombinase, particularly in the process of V-DJ rearrangements.
We next examined the transcriptional status of Ig genes as an indirect
reflection of the accessibility of these genes to the recombinase. Properly
spliced IgH transcripts of normal size were observed in stage IV and
surface Ig positive stage, but not in stage II nor III. However, IgH
transcripts of aberrant sizes were seen in stage II, III, and also IV.
Cross-lineage gene rearrangements were shown to occur frequently when
normally spliced IgH gene begins to be transcribed or just before this.
These findings may implicate that V-DJ or V-VDJ gene rearrangements forming
functional IgH genes, induce frequently TCR or TRG gene rearrangements. We
propose these dual genotypes are different in origin from those observed in
stem cell leukemia.
Volume 74,
Issue 1,
pp. 361-368,
07/01/1989
Copyright © 1989 by The American Society of Hematology
