Comparison of the immunoglobulin gene transcripts between immature B lineage acute lymphoblastic leukemia and the normal phenotypic counterparts in the bone marrow.
Immature B lineage acute lymphoblastic leukemia (ALL) is divided into two subtypes, 'pre-B' and 'early pre-B' ALL, by the presence or absence of cytoplasmic immunoglobulin (cIg). To study their clonal origin, we compared mu-chain transcripts in six cIg+ and eight cIg- ALL samples (CD10+/- CD19+ surface Ig-) with those in the normal phenotypic counterparts (CD10+ CD19+ surface Ig-) sorted from the bone marrow (BM). Northern blot analysis showed that the cIg+ ALL samples expressed greater amounts of mu-chain transcripts than the cIg- ALL samples. In the ALL samples and their counterparts, sequence analysis of mu-chain transcripts revealed infrequent somatic mutations of the V(H) genes and the similar usage of D and J(H) gene segments, but the length of complementarity determining region (CDR)-3 in the ALL samples was longer than that in the counterparts (50.0 +/- 15.5 vs 40.8 +/- 12.7 bp, P = 0.01). The mu-chain transcripts in the six cIg+ ALL samples and the counterparts (119/120 clones) had productive sequences, whereas those in the eight cIg- ALL samples had nonsense codons and/or frame shifts in their CDR-3. Our data suggest that a phenotype of ALL, 'pre-B' or 'early pre-B', is associated with V(H)-D-J(H) gene recombinatorial events, and that the CD10+ CD19+ surface Ig- population in the BM is not simply the cellular origin of ALL.
Mori
H
H
Department of Pediatrics, Nagoya University School of Medicine, Showa-ku, Japan.
Kiyoi
H
H
Horibe
K
K
Ohno
R
R
Naoe
T
T
D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D001853:Bone Marrow / Q000502:physiology*; D002051:Burkitt Lymphoma / Q000235:genetics*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006410:Hematopoiesis; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014158:Transcription, Genetic
D018941:Antigens, CD19; D007135:Immunoglobulin Variable Region; D007148:Immunoglobulin mu-Chains; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015260:Neprilysin