SKEWED REARRANGEMENT OF THE VH4-21 GENE DURING PRE-B ACUTE LYMPHOBLASTIC-LEUKEMIA

Thirty-six pre-B acute lymphoblastic leukemias (ALL) were studied for VH family expression. Among the 35 detected rearrangements, VHI family genes were expressed in 7, VH2 in 1, VH3 in 18, VH4 in 6 and VH6 in 3 . This expression is close to that expected according to the complexit y of the system. The complete sequence of the 6 VH4 genes was examined in order to determine whether there is a skewed rearrangement of indi vidual genes in this family. Our results indicate rearrangement of VH4 -21 in 3 cases, 71-4 in one, 58P2 in one case and probably of a new ge rminal VH4 gene for the sixth case. All the genes were displaying an a lmost complete homology with their germinal VH counterparts. The 6 seq uenced genes associated with 6 different D gene segments displaying a close homology with their germinal counterpart. JH4 segment was expres sed in 3 cases and JH6 in the remaining 3. These results associated wi th previous results obtained by others indicate that there is skewed r earrangement of the VH4-21 gene in pre-B ALL. It is presently unknown whether this phenomenon is the consequence of a selective process or w hether it reflects what normally occurs in the normal human functional repertoire, which could be more limited than the germline repertoire.