Apoptosis and interleukin 7 gene expression in chronic B-lymphocytic leukemia cells. 1995

B W Long, and P L Witte, and G N Abraham, and S A Gregory, and J M Plate
Department of Medicine, Rush-Presbyterian St. Luke's Medical Center, Chicago, IL 60612.

mRNA for interleukin 7 (IL-7) was readily detected in leukemic cells immediately upon their removal from patients with chronic B-lymphocytic leukemia (B-CLL). IL-7 mRNA expression and IL-7 gene transcription were down regulated, however, when B-CLL cells were placed in culture at 37 degrees C for 4 hr. Down regulation of the IL-7 gene was prevented in cells maintained at 4 degrees C. Continued culture of B-CLL cells at 37 degrees C resulted in programmed cell death, or apoptosis, as evidenced by DNA fragmentation. The coincident kinetics of IL-7 gene down regulation and apoptosis suggested that IL-7 gene expression may be required for maintenance of CLL viability in vivo. Signals for IL-7 gene regulation and apoptosis induction were thus examined. Activation of normal B cells through their immunoglobulin receptors did not result in upregulation of IL-7 gene expression. Reagents required for CLL cell purification and culture also did not contribute to IL-7 gene regulation and apoptosis induction. IL-7 gene expression was retained and apoptosis was prevented, however, in CLL cells cultured on a monolayer of EA.hy926 human umbilical cord endothelial hybrid cells. Signals specifically presented by EA.hy926 cells supported both CLL cell viability and IL-7 gene expression, whereas culture of CLL cells on A549/8 carcinoma cells, the fusion partner used to generate the EA.hy926 cells, did not. Cell-cell contact was required, as culture supernatants did not prevent apoptosis. Specifically, IL-7 mRNA expression was retained and apoptosis was prevented only by contact with the endothelial cell hybrids. Preliminary data indicated that integrins expressed on CLL cells affected modulation of apoptosis and IL-7 gene regulation, suggesting that integrins may play significant roles in regulating viability of CLL cells.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012334 RNA, Neoplasm RNA present in neoplastic tissue. Neoplasm RNA

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