ANALYSIS OF THE COMPLEMENTARY DETERMINING REGION-III OF THE IMMUNOGLOBULIN HEAVY-CHAIN LOCUS IN ACUTE LYMPHOBLASTIC-LEUKEMIA IN CHILEAN CHILDREN

We have analyzed the sequence of 40 VDJ rearrangements of the immunogl obulin heavy chain gene locus on 32 unselected children from Chile wit h precursor B cell ALL at diagnosis. Rearrangements were derived by PC R with VH gene family-specific primers and sequenced directly. The num ber of VDJ rearrangements, and the pattern of VH, DH and JH gene usage was identical to the one reported by groups from developed countries. CDR3 regions represented an unbiased repertoire; VH to JH joinings we re in frame in 36% of cases. Absent N nucleotides in the DJ border, su ggestive of fetal origin of ALL, were seen in 9/40 rearrangements but they did not correlate with younger age. More than one rearrangement w as sequenced in six patients, representing independent events with no signs of clonal evolution. One patient was analyzed at first bone marr ow relapse showing persistence of one rearrangement and evolution of a second one which conserved the DJ border. The subset of B cell precur sors which suffer malignant transformation to ALL appear to be common in different parts of the world.