The influence of recombinant human tumor necrosis factor alpha and its muteins used alone or in combination with 2-chlorodeoxyadenosine on normal and leukemic hematopoiesis in vitro.
We investigated the influence of TNF alpha and its muteins III, V and VI on the colony growth of normal and CML CFU-GM cells as well as on CFU-L clonogenic blasts from AML patients in cultures in vitro. The muteins were constructed using a synthetic cDNA fragment substituting nucleotides coding for the N-terminal amino acids in the chain of native TNF alpha. We observed that TNF alpha and mutein VI inhibited the growth of colonies formed by both types of CFU-GM and CFU-L cells in a greater degree than muteins III and V. In addition, the percentage of colony growth inhibition after the use of mutein VI was the greatest. These observations were the basis for the evaluation of interaction between 2-CdA and TNF alpha and between 2-CdA and mutein VI. We have confirmed that 2-CdA used together with mutein VI acts synergistically on CFU-GM and CFU-L cells, whereas 2-CdA and TNF alpha show the additive effect.
Korycka
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Department of Pharmacology, Medical University of Lódź, Poland.
Robak
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D000208:Acute Disease; D015703:Antigens, CD / Q000187:drug effects; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001853:Bone Marrow / Q000473:pathology; D017338:Cladribine / Q000494:pharmacology*; D004357:Drug Synergism; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D007951:Leukemia, Myeloid / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C109425:mutein 3; C109426:mutein 5; C105965:mutein 6; D017338:Cladribine