thymosin-beta(4) and Leukemia--Myeloid--Acute

We have compared the effects of AcSDKP, Thymosin beta4 (Tbeta4), MIP1alpha and TGFbeta on acute myeloid leukemia (AML) and B-lineage acute lymphoid leukemia (B-ALL) cells using liquid cultures in the presence of GM-CSF, IL-3 and SCF for AML cells and IL-3 and IL-7 for ALL cells. Each molecule was added daily and cell proliferation was evaluated on day 3 by thymidine incorporation. Whereas TGFbeta was found inhibitory in all the AML and B-ALL cases studied, MIP1alpha was inhibitory in 6/12 AML cases and had no effect on B-ALL cells. AcSDKP and Tbeta4 showed an inhibitory effect in a few cases but only at high doses which were inactive on normal cells. Thus, our study not only confirms the effect of TGFbeta, MIP1alpha and AcSDKP on AML cells but also provides new data concerning their effect on B-ALL and the possible inhibitory effect of AcSDKP at high doses. Furthermore, we show for the first time the effect of Tbeta4 on leukemic cells. Altogether, our data indicate differences of sensitivity of leukemic cells to negative regulators, some leukemias being inhibited by one or several of these molecules whereas others were unresponsive to all used. The clinical relevance of these observations still remains to be determined.

Topics: Adolescent; Adult; Aged; Burkitt Lymphoma; Cell Division; Chemokine CCL4; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Myeloid, Acute; Macrophage Inflammatory Proteins; Male; Middle Aged; Oligopeptides; Thymosin; Transforming Growth Factor beta; Tumor Cells, Cultured

A new analog of thymosin beta 4 has been isolated from tissues of several mammalian species. This peptide, designated thymosin beta 10, is composed of 42 amino acid residues and shows 75% sequence homology with thymosin beta 4. It occurs together with thymoxin beta 4 in a variety of tissues including spleen, liver, and thymus and also in several cultured cell lines. In the spleen of rat, mouse, cat, and man, the new peptide accounts for approximately 0.02% by weight of the total protein. In the calf it is replaced by another homologous peptide, designated thymosin beta 9, whose structure has been reported.

Topics: Amino Acid Sequence; Animals; Cats; Cell Line; Humans; Leukemia, Myeloid, Acute; Liver; Mice; Peptide Fragments; Rats; Species Specificity; Spleen; Structure-Activity Relationship; Thymosin; Thymus Gland; Tissue Distribution