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Blood, 15 November 2004, Vol. 104, No. 10, pp. 2997. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Prchal, J. T. Search for Related Content PubMed Articles by Prchal, J. T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Next Article  HEMATOPOIESIS Comment on Paglialunga et al, page 3148 G6PD activity is essential for definite erythropoiesis Josef T. Prchal BAYLOR COLLEGE OF MEDICINE Discovery of glucose 6-phosphate dehydrogenase (G6PD) deficiency has provided a foundation for modern hematology, and it has been a shining example of how discovery of the molecular basis of human diseases revolutionizes our understanding of biology and eventually changes how we practice medicine. The discovery of G6PD deficiency not only led to elucidation of X-chromosome inactivation by Beutler et al,1 and independently by Lyon,2 but was the first description of epigenetics. The concept of X-chromosome inactivation paved the way for studies of tumor clonality, elucidated the hierarchy of hematopoiesis, and provided an example of the heritability of a phenotype by mechanisms other than nucleotide sequence change. Yet, among the large number of mutants of G6PD, associated with either mild deficiency of the enzyme (causing acute intermittent hemolysis upon oxidant exposure) or more severe deficiency (causing a rare chronic hemolytic anemia), none is a null mutant. This has suggested that the absence of enzyme activity may not be compatible with life. In this issue of Blood, Paglialunga and colleagues examined the effect of the G6PD enzyme on development. They deleted the G6PD gene in mouse totipotent embryonic stem (ES) cells, and while this mutation was embryonically lethal, the ES cells were viable. When these mutated ES cells were induced to differentiation using an ingenious "hanging-drop culture method," cells of multiple lineages were produced, including cardiac cells, hepatocytes, mesodermal cells, and primitive erythroid cells, albeit with lower efficiency than cells with normal G6PD activity. However, primitive embryonic erythropoiesis seemed unable to undergo the essential developmental switch to definite erythropoiesis (see figure). WT and G6pd EB morphology. See the complete figure in the article beginning on page 3148.   Erythroid cells are subject to developmental control that is different in the yolk sac (embryonic erythropoiesis) than in fetal liver or adult bone marrow (definite or fetal/adult erythropoiesis). There are substantial developmental differences characterizing each stage, but the factors controlling the developmental switch have not been defined. For example, knock out of erythropoietin or erythropoietin receptor genes in mice allows the generation of erythroid cells in the yolk sac, but precludes the development of mature cells in the embryo leading to the fetal lethality.3 As shown by Paglialungaetal'spaper,after the switch of embryonic to definite (fetal/adult)erythropoiesis, the erythroid progenitors undergo apoptosis that can be abrogated, atleast in part, by reducing agents. This work demonstrates that there are more lessons to be learned from the study of G6PD, and the paper in this issue may provide an unexpected opening for better understanding of the developmental control of erythropoiesis. References Beutler E, Yeh M, Fairbanks VF. The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD deficiency as a marker. Proc Natl Acad Sci U S A. 1962;48: 9-16.[Free Full Text] Lyon MF. Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet. 1962;14: 135-148.[Medline] [Order article via Infotrieve] Kieran MW, Perkins AC, Orkin SH, Zon LI. Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor. Proc Natl Acad Sci U S A. 1996;93: 9126-9131.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: G6PD is indispensable for erythropoiesis after the embryonic-adult hemoglobin switch Francesca Paglialunga, Annalisa Fico, Ingram Iaccarino, Rosario Notaro, Lucio Luzzatto, Giuseppe Martini, and Stefania Filosa Blood 2004 104: 3148-3152. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Prchal, J. T. Search for Related Content PubMed Articles by Prchal, J. T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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