Expression of selected genes and oncogenes in differentiated HL-60 cells and primary cells from human leukemias.
cDNA clones complementary to mRNA of cells from patients with chronic lymphocytic leukemia (CLL) were used to examine quantitative changes in the mRNA levels of specific genes in human leukemia leukocytes. Twenty one CLL-positive clones that did not hybridize with placental mRNA were studied. These clones were significantly represented in the mRNA from leukemic leukocytes and were not represent in the mRNA from normal leukocytes. There was high level of expression of 7-2D gene in CLL and B lymphoma cells. RNA hybridizing with clone 7-3G was comparatively highly abundant in CCRF-CEM and EB virus transformed lymphoid cell, while clone 6-1E was highly represented in the mRNAs of Molt 3 and CCRF-CEM cells. The expression of three clones (6-1E, 7-3G and 9-5C) selected from a CLL cDNA library was studied by nucleic acid hybridization in human promyelocytic leukemia cell (HL-60) treated with chemical inducers of cell differentiation. The differentiation of HL-60 cells into macrophage-like cells upon induction by 12-o-tetradecanoylphorbol-13-acetate (TPA) was accompanied by rapid induction of the expression of 6-1E and 7-3G genes. The levels of expression of the 9-5C gene were not altered during macrophage-monocytic or granulocytic differentiation of HL-60 cells. The expression of the 6-1E and/or 7-3G gene was induced by TPA in four of 6 samples derived from patients who achieved complete remission, but not in any of the acute nonlymphocytic leukemia samples from patients who failed to achieve complete remission. These findings suggest that expression of the 6-1E and 7-3G genes is related to macrophage-monocytic differentiation and that alterations of these gene expressions in fresh leukemic cells after one hour of TPA treatment are of prognostic significance in predicting the response to treatment. The primary structure of a cDNA of a gene (6-1E) selectively expressed in CLL was determined. A computer search in the nucleotide sequence data bank did not identify this gene as any other gene. The 677 nucleotide mRNA is composed of a 384 nucleotide pol A tail. Moreover, the sequences of the other cDNA clones (1-6G, 5-2C,5-5G, 6-1G, 7-3G, 7-4A, 8-6G, and 9-5C) are not present in those of the data base of GenBank recorded up to 1988.(ABSTRACT TRUNCATED AT 400 WORDS)
Shiosaka
T
T
First Department of Internal Medicine, School of Medicine, Ehime University, Japan.
Tanaka
Y
Y
D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D009857:Oncogenes; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate