tretinoin and Leukemia--Lymphoid

The beginning of this century was marked, in our specialty as in other, by two revolutions: the routine use of molecular biology tools for a better prognosis of the disease (flt3 receptor duplication in AML, mutational profile of Ig genes in CLL, gene expression profile with ARN chips in aggressive lymphomas.), and the discovery of "intelligent" molecules, targeting the tumoral cell. In this category, the most appealing is the STI571 (Gleevec , Novartis), targeting the molecular abnormality of the cells expressing bcr-abl protein: CML, ALL Ph1(+). Other molecules targeting signal transduction proteins (ras farnesylation inhibitors for example) are already in clinical trials. The increasing therapeutic use of monoclonal antibodies is also to be cited, with a special mention concerning the rituximab, used in several B lymphoid pathologies, from lymphoma to autoimmune diseases. His very good tolerance permits his use in ambulatory patients, and his combination with chemotherapy or his linkage with radioactive elements render this molecule indispensable. The other side of these molecules is their incredibly high cost, explaining the uncontrolled expenses in 2001 of hospitals hosting hematology as well as oncology activities.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Hematopoietic Stem Cell Transplantation; Humans; Imatinib Mesylate; Immunotoxins; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Lymphoma; Myelodysplastic Syndromes; Piperazines; Pyrimidines; Tretinoin

The human acute promyelocytic leukemia cell line HL-60 is induced by retinoic acid (RA) and N,N-dimethylformamide (DMF) to differentiate into cells having many of the functional and morphologic characteristics of mature granulocytes. With normal human phagocytic cells there is both superoxide anion (O2-) production and chemotaxis in response to chemoattractants such as N-formyl-methionyl-leucyl-phenylalanine (FMLP). We have now found that although HL-60 cells induced with RA alone produce O2- in response to 12-0-tetradecanoyl-phorbol-13-acetate (TPA) they are deficient in FMLP-stimulated O2- production and chemotaxis. In contrast, HL-60 induced either with DMF or with a combination of 10 nmol/L RA and a T cell-derived lymphokine, differentiation-inducing activity (DIA), produce O2- and exhibit chemotaxis in response to FMLP. The basis for these results appears to be the concentration of cell surface chemotactic peptide receptors. Thus, untreated HL-60 and HL-60 induced with either RA alone or DIA alone do not have measurable levels of FMLP receptors, whereas HL-60 induced with a combination of RA and DIA has 5,400 receptors per cell. HL-60 induced with RA and DIA plus 1 mumol/L dexamethasone have 25,000 receptors per cell and have greater chemotactic activity than HL-60 induced with the combination of RA and DIA. Thus, differentiation of HL-60 to cells with many properties of normal phagocytes can be induced in vitro by physiologic substances.

Topics: Cell Adhesion; Cell Differentiation; Cell Line; Chemotaxis; Cytochalasin B; Dimethylformamide; Humans; Kinetics; Leukemia, Lymphoid; Lymphokines; N-Formylmethionine Leucyl-Phenylalanine; Phagocytes; Receptors, Formyl Peptide; Receptors, Immunologic; Superoxides; Tetradecanoylphorbol Acetate; Tretinoin

Serum transferrin (the iron binding protein) exerts its iron carrier function at the cell surface after binding to the appropriate receptor (TrR). In this work it is demonstrated that differentiating agents induce loss of TrR from the surface of three leukemic cell lines (Molt-3, HL-60 and K-562). Loss of TrR correlates with change in morphology and induction of phenotypic markers of the differentiated cells. Removal of the differentiating agent from the culture is followed by reexpression of TrR on the cell surface. The data presented in this paper suggest that TrR may play a regulatory role in cell differentiation and malignant transformation.

Topics: Butyrates; Butyric Acid; Cell Differentiation; Cell Line; Dimethyl Sulfoxide; DNA Replication; Heme; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Receptors, Cell Surface; Receptors, Transferrin; Tetradecanoylphorbol Acetate; Transferrin; Tretinoin

There is a marked increase in the activity of sialic acid lyase (N-acetylneuraminate lyase; EC 4.1.3.3; also known as sialic acid aldolase) in HL-60 cells induced to differentiate into macrophages by the phorbol ester, tetradecanoylphorbol 12-myristate 13 acetate (TPA). Exposure of HL-60 cells to retinoic acid, butyric acid or dimethyl sulfoxide has little or no effect. The level of the enzyme remains unaltered in HL-60 cells grown in the presence of an inactive analog of TPA, nor does it change in variants of HL-60 cells resistant to TPA.

Topics: beta-D-Galactoside alpha 2-6-Sialyltransferase; Butyrates; Butyric Acid; Cell Differentiation; Cell Line; Dimethyl Sulfoxide; Humans; Leukemia, Lymphoid; Oxo-Acid-Lyases; Phorbol Esters; Sialyltransferases; Tetradecanoylphorbol Acetate; Tretinoin

We have studied the effects of retinoic acid (RA) on bone marrow leukemic cells from children with acute nonlymphocytic leukemia (ANLL) at the time of diagnosis, and on cells from four ALL/lymphoma cell lines (common-ALL, pre-B-ALL, T-ALL, and Burkitt's lymphoma) derived from children with these diseases. Cells were cultured in methylcellulose medium with clinically attainable concentrations (0.25-2.0 microM) of RA for two weeks prior to colony and cluster quantitation. Myeloid progenitor cells (CFU-GM) obtained from children with hematologically normal bone marrows were also cultured with RA. Of 19 patients with ANLL whose cells formed colonies, 16 (84%) were inhibited by RA; three patients showed either increased or unchanged colony numbers with RA. RA had a similar effect on both ANLL cluster and colony growth. RA (1-2 microM) also inhibited colony growth of the pre-B-ALL, common-ALL, and Burkitt's lymphoma lines; the T-ALL line and normal bone marrow CFU-GM were not inhibited. The inhibitory effects of RA on pediatric ANLL bone marrow cells and on some ALL/lymphoma cell lines compared with CFU-GM indicate that RA may be of value in the treatment of these malignancies in children.

Topics: B-Lymphocytes; Bone Marrow; Burkitt Lymphoma; Cell Division; Cell Line; Child; Colony-Forming Units Assay; Hematopoietic Stem Cells; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; T-Lymphocytes; Tretinoin

Persisting human papilloma virus (HPV) 2 induced common warts of a chronic lymphatic leukemia patient were orally treated with aromatic retinoid Ro 10-9359 (Tigason). Clinically, the lesions improved rapidly. Virus-specific cytopathogenic effects (CPE), virus particles and viral DNA were no longer detectable. Therapy was discontinued because of the development of a liposarcoma, which led to a complete relapse of the cutaneous lesions. HPV-2 specific parameters, CPE and viral DNA, were restored. Comparison of the restriction enzyme cleavage patterns revealed that warts before and after therapy contained the same HPV-2 subtype. The implications of the observation on the effect of Tigason on virus-induced papillomas are discussed.

Topics: Administration, Oral; Aged; Etretinate; Hand; Humans; Leukemia, Lymphoid; Male; Skin Diseases; Tretinoin; Warts