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 immunoglobulin heavy chain gene locus on 32 unselected children from Chile with precursor B cell ALL at diagnosis. Rearrangements were derived by PCR with VH gene family-specific primers and sequenced directly. The number 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 were in frame in 36% of cases. Absent N nucleotides in the DJ border, suggestive of fetal origin of ALL, were seen in 9/40 rearrangements but they did not correlate with younger age. More than one rearrangement was sequenced in six patients, representing independent events with no signs of clonal evolution. One patient was analyzed at first bone marrow relapse showing persistence of one rearrangement and evolution of a second one which conserved the DJ border. The subset of B cell precursors which suffer malignant transformation to ALL appear to be common in different parts of the world.
Department of Pediatrics, Catholic University of Chile, Santiago.
F J
FJ
Barriga
C
C
RisueNo
J C
JC
Patillo
W
W
Andrade
M E
ME
Cabrera
V
V
Beressi
P
P
Del Borgo
C
C
Salgado
A
A
Becker
M
M
Campbell
P
P
Bertin
D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002677:Chile; D018076:DNA, Complementary; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains