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 sequence of the complementarity determining region III (CDRIII) in the rearranged immunoglobulin heavy chain gene (IgH) has been used as a molecular fingerprint to identify the leukemic cells. In a child with B-precursor ALL without central nervous system (CNS) disease at diagnosis and 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 the leukemic cells from the cerebrospinal fluid at relapse. Whereas two of the three IgH sequences isolated from the leukemic cells at CNS relapse 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 identified in the CNS differed from the marrow sequence only at the variable gene segment adjoining the CDRIII. Using a detection method based on the polymerase chain reaction, the altered IgH sequence identified in the 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 relapse. These findings indicate that the clonal pattern of leukemia in the CNS may differ from that in the marrow.
Wasserman
R
R
Division of Oncology, Children's Hospital of Philadelphia, PA 19104.
Felix
C A
CA
McKenzie
S E
SE
Shane
S
S
Lange
B
B
Finger
L R
LR
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology; D002648:Child; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008969:Molecular Sequence Data; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000276:immunology; D012008:Recurrence
D014408:Biomarkers, Tumor; D007135:Immunoglobulin Variable Region