{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:12:29Z","timestamp":1772082749734,"version":"3.50.1"},"reference-count":32,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vitamin A is a pivotal biochemical factor required for normal proliferation and differentiation as well as for specialized functions, such as vision. The dietary intake of 1500 IU\/day is recommended in the first year of life. Here, we report the case of an infant who had been given 62\u2009000 IU\/day for 80 days. The infant showed several clinical signs of retinol intoxication, including severe anemia and thrombocytopenia. Bone marrow showed a remarkably reduced number of erythroid and megakaryocytic cells. The interruption of vitamin A treatment was immediately followed by clinical and biochemical recovery. To clarify whether the effects of retinol are due to a direct action on bone marrow cell proliferation, we investigated the activity of retinol (both the drug and the pure molecule) on the growth of K-562, a multipotent hematopoietic cell line, and on bone marrow mesenchymal stem cells. We observed that vitamin A strongly inhibited the proliferation of the cells at concentrations similar to those reached in vivo. Subsequent biochemical analyses of the cell cycle suggested that the effect was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21Cip1 and p27Kip1. These are the first findings to demonstrate that infant hypervitaminosis A causes a severe anemia and thrombocytopenia and that this is probably due to the direct effect of the molecule on the growth of all bone marrow cellular components. Our data also suggest potential bone marrow functional alterations after excessive vitamin A intake because of emerging social habits.<\/jats:p>","DOI":"10.1182\/blood.v99.6.2017","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T21:48:18Z","timestamp":1033508898000},"page":"2017-2022","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":35,"title":["Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition"],"prefix":"10.1182","volume":"99","author":[{"given":"Silverio","family":"Perrotta","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Nobili","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Rossi","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Criscuolo","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Di Pinto","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Passaro","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Cennamo","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Oliva","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulvio","family":"Della Ragione","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Department of Biochemistry and Biophysics \u201cF. Cedrangolo,\u201d Second University of Naples, Naples, Italy; and the Institute of Pediatrics, University of Foggia, Foggia, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021300124570000_B1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1093\/ajcn\/49.2.358","article-title":"Safety of vitamin A.","volume":"49","author":"Bendich","year":"1989","journal-title":"Am J Clin Nutr."},{"key":"2020021300124570000_B2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/ajcn\/52.2.183","article-title":"Evaluation of vitamin A toxicity.","volume":"52","author":"Hathcock","year":"1990","journal-title":"Am J Clin Nutr."},{"key":"2020021300124570000_B3","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0190-9622(87)70133-9","article-title":"Hypervitaminosis A syndrome: a paradigm of retinoid side effects.","volume":"16","author":"Silverman","year":"1987","journal-title":"J Am Acad Dermatol."},{"key":"2020021300124570000_B4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.276.5309.71","article-title":"Marrow stromal cells as stem cells for nonhematopoietic tissues.","volume":"276","author":"Prockop","year":"1997","journal-title":"Science."},{"key":"2020021300124570000_B5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/mus.880181212","article-title":"Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine.","volume":"18","author":"Wakitani","year":"1995","journal-title":"Muscle Nerve."},{"key":"2020021300124570000_B6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1006\/exnr.2000.7389","article-title":"Adult bone marrow stromal cells differentiate into neural cells in vitro.","volume":"164","author":"Sanchez-Ramos","year":"2000","journal-title":"Exp Neurol."},{"key":"2020021300124570000_B7","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/1097-4547(20000815)61:4<364::AID-JNR2>3.0.CO;2-C","article-title":"Adult rat and human bone marrow stromal cells differentiate into neurons.","volume":"61","author":"Woodbury","year":"2000","journal-title":"J Neurosci Res."},{"key":"2020021300124570000_B8","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1182\/blood.V88.4.1168.bloodjournal8841168","article-title":"Cytokine regulation of proliferation and cell adhesion are correlated events in human CD34+ hemopoietic progenitors.","volume":"88","author":"Levesque","year":"1996","journal-title":"Blood."},{"key":"2020021300124570000_B9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3181\/00379727-212-44021","article-title":"Adhesive interactions in the hematopoietic system: regulation by cytokines.","volume":"212","author":"Fernandez","year":"1996","journal-title":"Proc Soc Exp Biol Med."},{"key":"2020021300124570000_B10","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1089\/152581600750062264","article-title":"Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages.","volume":"9","author":"Majumdar","year":"2000","journal-title":"J Hematother Stem Cell Res."},{"key":"2020021300124570000_B11","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1089\/152581600750062228","article-title":"Perspectives on the morphology and biology of CD34-negative stem cells.","volume":"9","author":"Huss","year":"2000","journal-title":"J Hematother Stem Cell Res."},{"key":"2020021300124570000_B12","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1056\/NEJM197604082941503","article-title":"Vitamin A transport in human vitamin A toxicity.","volume":"294","author":"Smith","year":"1976","journal-title":"N Engl J Med."},{"key":"2020021300124570000_B13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1182\/blood.V45.3.321.321","article-title":"Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.","volume":"45","author":"Lozzio","year":"1975","journal-title":"Blood."},{"key":"2020021300124570000_B14","first-page":"357","article-title":"Heterogeneity in the cellular commitment of a human leukemic cell line: K 562.","volume":"7","author":"Vainchenker","year":"1981","journal-title":"Blood Cells."},{"key":"2020021300124570000_B15","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1073\/pnas.86.8.2849","article-title":"Induction of megakaryocytic differentiation and modulation of protein kinase gene expression by site-selective cAMP analogs in K-562 human leukemic cells.","volume":"86","author":"Tortora","year":"1989","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021300124570000_B16","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S0301-472X(00)00553-1","article-title":"Overexpression of GATA-2 inhibits erythroid and promotes megakaryocyte differentiation.","volume":"28","author":"Ikonomi","year":"2000","journal-title":"Exp Hematol."},{"key":"2020021300124570000_B17","first-page":"83","article-title":"Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method.","volume":"2","author":"Friedenstein","year":"1974","journal-title":"Exp Hematol."},{"key":"2020021300124570000_B18","first-page":"827","article-title":"5\u2032-Deoxy-5\u2032-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines.","volume":"10","author":"Della Ragione","year":"1995","journal-title":"Oncogene."},{"key":"2020021300124570000_B19","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1006\/bbrc.2000.2161","article-title":"Pyrrolidine dithiocarbamate induces apoptosis by a cytochrome c-dependent mechanism.","volume":"268","author":"Della Ragione","year":"2000","journal-title":"Biochem Biophys Res Commun."},{"key":"2020021300124570000_B20","doi-asserted-by":"crossref","first-page":"15942","DOI":"10.1074\/jbc.271.27.15942","article-title":"Biochemical characterization of p16INK4- and p18-containing complexes in human cell lines.","volume":"271","author":"Della Ragione","year":"1996","journal-title":"J Biol Chem."},{"key":"2020021300124570000_B21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/0092-8674(94)90379-4","article-title":"p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest.","volume":"76","author":"Dulic","year":"1994","journal-title":"Cell."},{"key":"2020021300124570000_B22","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/j.1460-2075.1992.tb05135.x","article-title":"Cyclin A is required at two points in the human cell cycle.","volume":"11","author":"Pagano","year":"1992","journal-title":"EMBO J."},{"key":"2020021300124570000_B23","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1073\/pnas.89.7.2824","article-title":"Human cyclin-dependent kinase 2 is activated during the S and G2 phases of the cell cycle and associates with cyclin A.","volume":"89","author":"Rosenblatt","year":"1992","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021300124570000_B24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1006\/bbrc.1998.9263","article-title":"Resveratrol arrests the cell division cycle at S\/G2 phase transition.","volume":"250","author":"Della Ragione","year":"1998","journal-title":"Biochem Biophys Res Commun."},{"key":"2020021300124570000_B25","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0140-6736(84)90781-5","article-title":"Vitamin-A-induced anaemia.","volume":"2","author":"White","year":"1984","journal-title":"Lancet."},{"key":"2020021300124570000_B26","first-page":"705","article-title":"Thrombocytopenia caused by isotretinoin.","volume":"70","author":"Hesdorffer","year":"1986","journal-title":"S Afr Med J."},{"key":"2020021300124570000_B27","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/S0190-9622(87)80276-1","article-title":"Isotretinoin-induced thrombocytopenia.","volume":"5","author":"Johnson","year":"1987","journal-title":"J Am Acad Dermatol."},{"key":"2020021300124570000_B28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1651-2227.1965.tb06345.x","article-title":"Chronic vitamin A intoxication during the first half year of life: description of 5 cases.","volume":"54","author":"Persson","year":"1965","journal-title":"Acta Paediatr Scand."},{"key":"2020021300124570000_B29","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/jn\/115.7.929","article-title":"The interaction of dietary vitamin A and vitamin D related to skeletal development in turkey poult.","volume":"115","author":"Metz","year":"1985","journal-title":"J Nutr."},{"key":"2020021300124570000_B30","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/S0022-3476(47)80138-6","article-title":"Comparative absorption, excretion, and storage of oily and aqueous preparations of vitamin A.","volume":"31","author":"Lewis","year":"1947","journal-title":"J Pediat."},{"key":"2020021300124570000_B31","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1182\/blood.V95.2.470","article-title":"All-trans retinoic acid enhances the long-term repopulating activity of cultured hematopoietic stem cells.","volume":"95","author":"Purton","year":"2000","journal-title":"Blood."},{"key":"2020021300124570000_B32","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1006\/excr.1999.4735","article-title":"Cell cycle arrest induced by the vitamin D(3) analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27.","volume":"254","author":"Park","year":"2000","journal-title":"Exp Cell Res."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/99\/6\/2017\/1681718\/2017.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/99\/6\/2017\/1681718\/2017.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T05:12:58Z","timestamp":1581570778000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/99\/6\/2017\/53568\/Infant-hypervitaminosis-A-causes-severe-anemia-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,3,15]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2002,3,15]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v99.6.2017","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2002,3,15]]}}}