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

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.