[Effects of interferon-gamma combined with all-trans retinoic acid on proliferation and differentiation of leukemia cell lines NB4 and MR2]. 2006

Peng-Cheng He, and Mei Zhang, and Di Wu, and Hui Xu, and Rui-Bo Cai, and Ya-Lin Liu
Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P. R. China.

OBJECTIVE More than 90% patients with acute promyelocytic leukemia (APL) achieve clinical complete remission by using all-trans retinoic acid (ATRA). However, the rapid development of ATRA-resistance has become a problem in treating APL. Many researches indicate that the mechanism of ATRA-resistance is related to lack of some proteins synthesized by interferon (IFN). This study was to explore the possibility and the possible mechanism of treating ATRA-resistant APL with IFN in combination with ATRA. METHODS Interferon-gamma (IFNgamma) alone or IFNgamma combined with ATRA was used to treat ATRA-sensitive cell line NB4 and ATRA-resistant cell line MR2. Cell proliferation was tested by MTT assay. Light microscope and NBT test were used to evaluate cell differentiation. The expression of promyelocytic leukemia (PML) protein was observed by indirect immune fluorescent method. RESULTS On the 8th day, the growth inhibition rates of NB4 cells and MR2 cells were significantly higher in combination group than in IFNgamma group and ATRA group (95.2% vs. 68.0% and 85.0%, P<0.05; 51.5% vs. 24.1% and 4.3%, P<0.05). On the 3rd day, the positive rates of NBT in NB4 cells and MR2 cells were significantly higher in combination group than in IFNgamma group and ATRA group (93.3% vs. 19.3% and 74.7%, P<0.05; 31.5% vs. 16.8% and 5.2%, P<0.05). After treatment of IFNgamma, the fluorescent particles in NB4 and MR2 cell nuclei were obviously increased as compared with those in control group. CONCLUSIONS IFNgamma and ATRA have synergistic inhibitory effect on the proliferation of NB4 cells and MR2 cells, and can partially induce the differentiation of ATRA-resistant MR2 cells.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071156 Promyelocytic Leukemia Protein A tripartite motif protein that contains three ZINC FINGERS, including a RING FINGER DOMAIN, at its N-terminal. Several nuclear and one cytoplasmic isoforms result from alternative splicing of the PML gene; most nuclear isoforms localize to subnuclear structures (PML nuclear bodies) that are disrupted in ACUTE PROMYELOCYTIC LEUKEMIA cells. RNF71 Protein,TRIM19 Protein
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D014212 Tretinoin An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE). Retinoic Acid,Vitamin A Acid,Retin-A,Tretinoin Potassium Salt,Tretinoin Sodium Salt,Tretinoin Zinc Salt,Vesanoid,all-trans-Retinoic Acid,beta-all-trans-Retinoic Acid,trans-Retinoic Acid,Acid, Retinoic,Acid, Vitamin A,Acid, all-trans-Retinoic,Acid, beta-all-trans-Retinoic,Acid, trans-Retinoic,Potassium Salt, Tretinoin,Retin A,Salt, Tretinoin Potassium,Salt, Tretinoin Sodium,Salt, Tretinoin Zinc,Sodium Salt, Tretinoin,Zinc Salt, Tretinoin,all trans Retinoic Acid,beta all trans Retinoic Acid,trans Retinoic Acid
D015473 Leukemia, Promyelocytic, Acute An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION. Leukemia, Myeloid, Acute, M3,Leukemia, Progranulocytic,Myeloid Leukemia, Acute, M3,Progranulocytic Leukemia,Promyelocytic Leukemia, Acute,AML M3,Acute Promyelocytic Leukemia,Leukemia, Acute Promyelocytic,M3 ANLL,ANLL, M3,Acute Promyelocytic Leukemias

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