IDENTIFICATION OF AN ALTERED IMMUNOGLOBULIN HEAVY-CHAIN GENE REARRANGEMENT IN THE CENTRAL-NERVOUS-SYSTEM IN B-PRECURSOR ACUTE LYMPHOBLASTIC-LEUKEMIA

In B-precursor acute lymphoblastic leukemia (ALL), the nucleotide sequ ence of the complementarity determining region III (CDRIII) in the rea rranged immunoglobulin heavy chain gene (IgH) has been used as a molec ular fingerprint to identify the leukemic cells. In a child with B-pre cursor ALL without central nervous system (CNS) disease at diagnosis a nd a subsequent isolated CNS relapse, we examined the stability of the rearranged IgH by comparing the nucleotide sequences of the CDRIII in the leukemic cells from the marrow at diagnosis to the sequences in t he leukemic cells from the cerebrospinal fluid at relapse. Whereas two of the three IgH sequences isolated from the leukemic cells at CNS re lapse were identical to sequences originally isolated from the marrow lymphoblasts at diagnosis, the third CNS sequence was similar but not identical to the third marrow sequence. The third IgH sequence identif ied in the CNS differed from the marrow sequence only at the variable gene segment adjoining the CDRIII. Using a detection method based on t he polymerase chain reaction, the altered IgH sequence identified in t he leukemic cells from the cerebrospinal fluid was noted to be present in the CNS at a higher frequency than the related diagnostic sequence and was not detected in the marrow either at diagnosis or at CNS rela pse. These findings indicate that the clonal pattern of leukemia in th e CNS may differ from that in the marrow.