thymosin-beta(4) and Leukemia

Thymosin beta 4 (beta 4) is an ubiquitous 5-kDa peptide that has been identified as an actin-sequestering peptide. In this work, Northern blot analysis was used to study the beta 4 mRNA levels during the cell cycle of rat thymocytes and hepatocytes as well as in human lymphocytes from patients with leukemia. beta 4 mRNA was found in all the stages of thymocyte and hepatocyte cell cycle, showing an increase in the S-phase which was maintained during the G2 and M phases. Incubation of splenic T-cells with concanavalin A, phorbol myristate acetate or the ionophore A23187 lead to a similar increase of beta 4 transcript during the S-phase. The increase in beta 4 mRNA observed in the G2/M boundary of the cell cycle, together with its ability to inhibit actin polymerization, suggests a possible role of beta 4 in the the morphological changes and actin redistribution occurring during the cytokinesis.

Topics: Actins; Animals; Calcimycin; Cell Division; Concanavalin A; Gene Expression; Humans; Leukemia; Liver; Liver Regeneration; Lymphocytes; Peptides; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tetradecanoylphorbol Acetate; Thymosin; Thymus Gland; Time Factors

Thymosin beta 4 (T beta 4) was originally isolated as a thymic hormone. Its functional properties remain obscure; however, the N-terminal peptidic sequence could have a regulatory function on hematopoietic stem cell proliferation. To investigate the mechanism of T beta 4 expression, we studied T beta 4 gene expression in various leukemic cells and in established cell lines. Among leukemic cell samples obtained from leukemia patients, the T beta 4 gene was highly expressed in a lymphoid lineage, especially in adult T-cell leukemia (ATL) cells, rather than in a granulocyte lineage. The T beta 4 gene was more transcriptionally active in chronic B-cell leukemia than in acute B-cell leukemia, while it was inactive in plasma cell leukemia. We also found that cells from one of the ATL patients transcribed a heterogeneous message. T beta 4 messenger RNA increased in MOLT-3 during differentiation by 12-O-tetradecanoylphorbol-13-acetate (TPA), in HL60 cells induced by TPA or dimethylsulfoxide and K562 cells stimulated by cytosine arabinoside or hemin. The genomic sequence of T beta 4 is considered to be highly conserved. Only 1 of 20 genomes from normal or hematopoietic malignant cells showed restriction fragment length polymorphism. These findings, along with previous data, suggest that T beta 4 may be a new marker of differentiation of hematopoietic cells.

Topics: Adult; Cell Differentiation; Cell Line; Female; Gene Expression Regulation; Hematopoietic Stem Cells; Humans; Kinetics; Leukemia; Leukocytes; Male; Middle Aged; Reference Values; RNA, Messenger; Tetradecanoylphorbol Acetate; Thymosin; Transcription, Genetic