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 alpha beta lineage
T. Szczepanski et al., 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 alpha beta lineage, BLOOD, 93(12), 1999, pp. 4079-4085
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, resp
ectively. IGH gene rearrangements were found in 19% (13/69) of CD3(-) T-ALL
and in 50% of TCR gamma delta(+) T-ALL (12/24), whereas only a single TCR
alpha beta(+) T-ALL (1/25) displayed a monoallelic IGH gene rearrangement.
The association with the T-cell receptor (TCR) phenotype was further suppor
ted by the striking relationship between IGH and TCR delta (TCRD) gene rear
rangements, ie, 32% of T-ALL (23/72) with monoallelic or biallelic TCRD gen
e rearrangements had IGH gene rearrangements, whereas only 1 of 26 T-ALL wi
th biallelic TCRD gene deletions contained a monoallelic IGH gene rearrange
ment. 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 3
2 (82%) DH-JH rearrangements. Whereas the usage of VH gene segments was see
mingly random, preferential usage of DH6-19 (45%) and DH7-27 (21%) gene seg
ments was observed. Although the JH4 and JH6 gene segments were used most f
requently (33% and 21%, respectively), a significant proportion of joinings
(28%) used the most upstream JH1 and JH2 gene segments, which are rarely u
sed in precursor-B-ALL and normal B cells (1% to 4%). In conclusion, the hi
gh 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 rearrangement
s in immature (non-TCR alpha beta(+)) T-ALL as a result of continuing V(D)J
recombinase activity. More mature cup-lineage T-ALL with biallelic TCRD ge
ne deletions apparently have switched off their recombination machinery and
are less prone to crosslineage IGH gene rearrangements. The combined resul
ts indicate that IGH gene rearrangements in T-ALL are post-oncogenic proces
ses, which are absent in T-ALL with deleted TCRD genes and completed TCR al
pha (TCRA) gene rearrangements. (C) 1999 by The American Society of Hematol
ogy.