thymosin and Leukemia--Myeloid--Acute

To investigate the expression and activity regulation of indoleamine 2,3-dioxygenase(IDO) in acute myeloid leukemia cells.. Expression of IDO and TLR9 in HL-60 and K562 cells cocultured with or without IFN-γ,Tα1,IFN-γ+Tα1 and chloroquine were determined by reverse transcription-polymerase chain reaction(RT-PCR). Then, the IDO activity in HL-60 and K562 cells cocultured with or without IFN-γ,Tα1,IFN-γ+ Tα1 was assayed by coomassie brilliant blue staining and modified colorimetric method.. Both IDO and TLR9 mRNA were expressed in HL-60 and K562 cells; IFN-γ increased the expression and activity of IDO in a concentration-dependent manner; Tα1 decreased the expression and activity of IDO in a concentration-dependent manner; the up-regulation of IFN-γ on IDO induced expression and activity had been weakened by Tα1(P<0.01); Chloroquine had no effect on the expression of IDO. The expression of TLR9 in HL-60 cells and K562 cells cocultured with IFN-γ,Tα1,IFN-γ+Tα1 and chloroquine was not significantly changed.. IDO can be expressed in acute myeloid leukemia cells and possesses the activity. IDO may play an important role in immune tolerance induced by leukemia cells, and become a new predictor of AML prognosis. Tα1 decreases the expression and activity of IDO, which can weaken the induction of IFN-γ on IDO expression and activity, thus Tα1 as an immune modulator may be a new agent for AML immunotherapy.

Topics: Cell Count; Cells, Cultured; Coculture Techniques; HL-60 Cells; Humans; Immune Tolerance; Indoleamine-Pyrrole 2,3,-Dioxygenase; Indoles; Interferon-gamma; Leukemia, Myeloid, Acute; Prognosis; RNA, Messenger; Thymalfasin; Thymosin

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

More than 1 year is required for immunologic function to recover following human marrow grafting. In an attempt to shorten the time required for immunologic reconstitution, 14 patients were treated with thymosin fraction 5 after transplantation. Two died before administration of thymosin could be completed. In the remaining 12 patients, immunologic studies were compared to those of patients who were transplanted but did not receive thymosin. While five patients had transient elevation of in vitro lymphocyte blastogenesis during thymosin treatment, results of other immunologic studies from patients treated with thymosin were similar to those from patients not treated. The subsequent development of graft-versus-host disease, major or minor infection, and leukaemic relapse was not different between the groups. Six patients are alive and five are well without problems; one has chronic graft-versus-host disease. We conclude that thymosin fraction 5 administered as described was not toxic. Although modifying some immunological parameters, thymosin did not appear to alter the incidence of graft-versus-host disease, infection or leukaemic relapse or to accelerate immunologic reconstitution.

Topics: Adolescent; Adult; Anemia, Aplastic; Antibody Formation; Bone Marrow Transplantation; Child; Graft vs Host Disease; Humans; Immunity, Cellular; Immunoglobulins; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphocyte Activation; Rosette Formation; Thymalfasin; Thymosin; Time Factors

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