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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4079-4085
RAPID COMMUNICATION
Ig Heavy Chain Gene Rearrangements in T-Cell Acute Lymphoblastic
Leukemia Exhibit Predominant DH6-19 and DH7-27 Gene
Usage, Can Result in Complete V-D-J Rearrangements, and Are Rare in
T-Cell Receptor   Lineage
Tomasz Szczepanski,
Marja J. Pongers-Willemse,
Anton W. Langerak,
Wietske A. Harts,
Annemarie J.M. Wijkhuijs,
Elisabeth R. van Wering, and
Jacques J.M. van Dongen
From the Department of Immunology, University Hospital
Rotterdam/Erasmus University Rotterdam, Rotterdam, The Netherlands; the
Department of Pediatric Hematology and Chemotherapy, Silesian Medical
Academy, Zabrze, Poland; and the Dutch Childhood Leukemia Study Group,
The Hague, The Netherlands.
Rearranged IGH genes were detected by Southern blotting in
22% of 118 cases of T-cell acute lymphoblastic leukemia (ALL) and involved monoallelic and biallelic rearrangements in 69% (18/26) and
31% (8/26) of these cases, respectively. IGH gene
rearrangements were found in 19% (13/69) of CD3 T-ALL
and in 50% of TCR  + T-ALL (12/24), whereas only a
single TCR  + T-ALL (1/25) displayed a monoallelic
IGH gene rearrangement. The association with the T-cell
receptor (TCR) phenotype was further supported by the striking
relationship between IGH and TCR delta (TCRD) gene
rearrangements, ie, 32% of T-ALL (23/72) with monoallelic or biallelic
TCRD gene rearrangements had IGH gene rearrangements, whereas only 1 of 26 T-ALL with biallelic TCRD gene deletions contained a monoallelic IGH gene rearrangement. Heteroduplex
polymerase chain reaction (PCR) analysis with VH and
DH family-specific primers in combination with a JH
consensus primer showed a total of 39 clonal products, representing 7 (18%) VH-(DH-)JH joinings and 32 (82%)
DH-JH rearrangements. Whereas the usage of
VH gene segments was seemingly random, preferential usage of
DH6-19 (45%) and DH7-27 (21%) gene segments was
observed. Although the JH4 and JH6 gene segments were
used most frequently (33% and 21%, respectively), a significant
proportion of joinings (28%) used the most upstream JH1 and
JH2 gene segments, which are rarely used in precursor-B-ALL and normal B cells (1% to 4%). In conclusion, the high frequency of
incomplete DH-JH rearrangements, the frequent usage
of the more downstream DH6-19 and DH7-27 gene
segments, and the most upstream JH1 and JH2 gene
segments suggests a predominance of immature IGH rearrangements
in immature (non-TCR+) T-ALL as a result of
continuing V(D)J recombinase activity. More mature -lineage T-ALL
with biallelic TCRD gene deletions apparently have switched off
their recombination machinery and are less prone to cross-lineage
IGH gene rearrangements. The combined results indicate that
IGH gene rearrangements in T-ALL are postoncogenic processes, which are absent in T-ALL with deleted TCRD genes
and completed TCR alpha (TCRA) gene rearrangements.
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