tretinoin and Leukemia--Hairy-Cell

The aim of differentiation therapy is to induce a maturation of the leukemic clone. Various approaches have been used: suppression of proliferation by low dose Ara-C in acute myeloid leukemia (AML); enhancement of differentiation by retinoic acid derivatives in acute promyelocytic leukemia (APL) or by differentiation-inducing factors; modulation of cell metabolism by breaking an autocrine loop in hairy cell leukemia (HCL). In all cases the treatment is given continuously at small doses over a long period of time. The very significant clinical results which have been obtained mainly in APL with all-trans retinoic acid and in HCL with alpha-interferon are briefly discussed.

Topics: Cell Differentiation; Cytarabine; Humans; Interferon Type I; Leukemia; Leukemia, Hairy Cell; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes; Tretinoin

Differentiation therapies try to change the malignant cell in order to acquire a more mature or normal phenotype. Various ways were tested in leukemia: suppression the proliferative pressure by low dose Ara-C, enhancement of the differentiation by retinoic acid derivatives or by differentiation factors, and modulation of the cell metabolism interrupting an autocrine loop (a growth factor and its receptor). The treatment is given continuously at small doses, during a long period of time. In all these cases it seems necessary to tailor the differentiation therapy to each category of leukemia.

Topics: Cell Differentiation; Cell Division; Cytarabine; Humans; Interferon Type I; Leukemia; Leukemia, Hairy Cell; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes; Tretinoin

B-Chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) are both differentiated B-cell lymphoproliferative disorders. Prior studies have suggested that phorbol esters and the macrocyclic lactone Bryostatin-1, which are both protein kinase-C activators, can induce the differentiation of B-CLL cells into HCL cells in vitro, as evidenced by morphology, phenotype and TRAP activity. The differentiating effect of all-trans retinoic acid on B-CLL cells has been less extensively studied. We studied the effects of incubating adherence purified B-CLL cells with phorbol myristic acetate (PMA), all-trans retinoic acid (ATRA), and Bryostatin-1. None of these agents induced a true HCL phenotype (CD5-, CD11c/CD25 coexpression) under the conditions studied.

Topics: Acid Phosphatase; Antigens, CD; Antigens, Neoplasm; B-Lymphocytes; Biomarkers, Tumor; Bryostatins; Cell Differentiation; Enzyme Activation; Humans; Immunophenotyping; Isoenzymes; Lactones; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Macrolides; Neoplastic Stem Cells; Protein Kinase C; Tartrate-Resistant Acid Phosphatase; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Cells, Cultured

A cell line (CJ18) has been established from the peripheral blood of a patient with hairy cell leukaemia (HCL) in a leukaemic phase. They grow slowly in large clumps with a doubling time of 3-4 d. 8% show positivity for surface immunoglobulin G and a small percentage (5%) are positive for intracytoplasmic immunoglobulin. They are B1,Ia1 positive and CALL, TdT and OKM1 negative. Although they are Epstein Barr Virus Nuclear Antigen (EBNA) positive they have several features not found in other EBNA positive B lymphoblastoid cell lines which suggest they may be derived from the patient's leukaemic hairy cells. They are strongly positive for tartrate resistant acid phosphatase, esterase positive, contain numerous lysosomes and are able to phagocytose sheep red blood cells after exposure to tetradecanoyl-12, 13-phorbol acetate (TPA). Following exposure to retinoic acid and TPA they adhere to plastic with numerous slender processes, a feature seen in HCL cells.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Antigens, Viral; Cell Differentiation; Cell Line; Dimethyl Sulfoxide; Epstein-Barr Virus Nuclear Antigens; Humans; Karyotyping; Leukemia, Hairy Cell; Male; Microscopy, Electron; Middle Aged; Phagocytosis; Receptors, Antigen, B-Cell; Tetradecanoylphorbol Acetate; Tretinoin

Hairy cell leukaemia (HCL) cells on exposure to the tumour promoter tetradecanoyl-12,13-phorbol acetate (TPA) undergo a striking morphological change in culture, with the formation of long, slender cytoplasmic processes, and adhere to the plastic surface. By time lapse photography this change is seen to start within 10 min of exposure to the TPA and is characterised by slow but continuous extension and retraction of the processes. Apparent phagocytosis of sheep red cells but not of sensitised human red cells occurs. This response to TPA is prevented by cytochalasin D but not by 13 cis-retinoic acid. Lymphocytes from normal individuals and patients with chronic lymphocytic leukaemia and lymphoblasts from a patient with acute lymphoblastic leukaemia reacted by adhering to each other in small aggregates but did not adhere to the plastic surface. Monocytes adhere to plastic surfaces and respond to TPA by extension and retraction of cytoplasmic folds differing from the long slender processes formed by the HCL cells. Thus HCL cells are different in their response to TPA from both normal lymphocytes and monocytes.

Topics: Cells, Cultured; Cytochalasin D; Cytochalasins; Drug Interactions; Humans; Leukemia, Hairy Cell; Phagocytosis; Phorbols; Photography; Tetradecanoylphorbol Acetate; Time Factors; Tretinoin