Transcripts of immunoglobulin germline mu: an amplified myeloid and B-lymphoid common gene program in various leukemias.
To investigate the clinical implications of germline C mu transcription, the splice region between the 3' end of the enhancer and the first exon of immunoglobulin germline mu; was analyzed by RT-PCR in 63 samples from 59 patients with leukemia. Immunophenotypes of 33 samples from patients with acute leukemia were analyzed using a panel of these monoclonal antibodies: anti-immature/stem cell (HLA-DR, CD34); anti-mature myeloid (CD33, CD15); anti-T lymphoid (CD2, CD3, CD5, CD7, CD8), and anti-B lymphoid (CD10, CD19, CD20). Of the 63 samples, 33 (52%) contained germline C mu transcripts: 2/2 patients with chronic lymphocytic leukemia; 17/26 (65.4%) patients with acute myeloblastic leukemia; all 4 patients with chronic myelogenous leukemia in blast crisis and 1 in accelerated phase; 9/12 patients with acute lymphocytic leukemia. A clear correlation between germline transcripts and HLA-DR expression was observed among germline-positive cases (p < 0. 01). C mu expression and response to therapy clearly indicated that germline-mu-positive leukemia patients responded poorly to chemotherapy and had a worse clinical prognosis compared with C mu-negative patients (p < 0.01). After two courses of chemotherapy, 7/9 C mu-negative patients achieved complete remission compared to only 7/29 C mu-positive patients (p < 0.01). We conclude that the gene-regulating immunoglobulin germline C mu may be amplified in myeloid and B-lymphoid cells during leukemogenesis. Such genetic changes may be correlated with cellular terminal differentiation injury, resistance to chemotherapy and uncontrolled malignant cell proliferation.
Dong
L
L
Department of Hematology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
Guo
M
M
Huang
S M
SM
Jia
S Q
SQ
Wang
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification / Q000235:genetics* / Q000276:immunology; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics / Q000276:immunology; D005803:Genes, Immunoglobulin / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D016130:Immunophenotyping; D015448:Leukemia, B-Cell / Q000235:genetics* / Q000276:immunology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012334:RNA, Neoplasm / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
D007135:Immunoglobulin Variable Region; D015345:Oligonucleotide Probes; D012334:RNA, Neoplasm