Responses of hemopoietic precursors to 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 in the myelodysplastic syndromes
Autor: | Rodman Morgan, Grant Swanson, Peter L. Greenberg, Frederick Hecht, Vincent J. Picozzi |
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Rok vydání: | 1986 |
Předmět: |
Adult
Male medicine.medical_specialty Myeloid Immunology Retinoic acid Chromosome Disorders Tretinoin Biology Biochemistry Colony-Forming Units Assay chemistry.chemical_compound Calcitriol Bone Marrow Internal medicine Precursor cell hemic and lymphatic diseases medicine Humans Clonogenic assay Child Aged Chromosome Aberrations Clinical Trials as Topic Myelodysplastic syndromes Cell Biology Hematology Middle Aged medicine.disease Hematopoietic Stem Cells In vitro Hematopoiesis Haematopoiesis Endocrinology medicine.anatomical_structure chemistry Multipotent Stem Cell Myelodysplastic Syndromes Cancer research Female Cell Division |
Zdroj: | Blood. 67:1154-1161 |
ISSN: | 1528-0020 0006-4971 |
Popis: | To determine the effects of the “maturation-inducing” agents 13-cis retinoic acid and 1,25 dihydroxyvitamin D3 on marrow cells from normal individuals and patients with myelodysplastic syndromes (MDS), we assessed marrow hemopoietic clonogenicity and differentiation response patterns to these agents. These vitamins caused increased proliferation in vitro of normal clonogenic marrow myeloid precursor cells (CFU-GM), decreased erythroid precursors (BFU-E), and no change in multipotent stem cells (CFU-GEMM). Marrow hemopoietic colony-forming cell incidence was generally subnormal in the 22 MDS patients evaluated. In vitro exposure to both agents caused various patterns of alteration of MDS hemopoietic colony and cluster formation, with similar but more pronounced effects evoked by retinoic acid. In the vast majority of MDS patients, enhanced marrow clonal granulocyte-monocyte differentiation and decreased BFU-E growth were noted after in vitro exposure to these vitamins. Correlation of biological effects was demonstrated between in vivo changes of peripheral neutrophil counts and in vitro responses of myeloid precursors for ten MDS patients treated with an eight-week therapeutic course of retinoic acid. Cytogenetic analyses indicated persisting aneuploidy or coexisting normal and aneuploid karyotypes in the cultured MDS myeloid cells and (with one exception) in native marrow cells from the treated patients. The varying responses of the MDS cells may monitor differing proportions of normal versus leukemic marrow cells susceptible to proliferative and differentiative expression on exposure to these agents. |
Databáze: | OpenAIRE |
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