{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:46:37Z","timestamp":1770885997465,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,5,9]],"date-time":"2010-05-09T00:00:00Z","timestamp":1273363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>One of the cardinal symptoms of type 1 Gaucher Disease (GD) is cytopenia, usually explained by bone marrow (BM) infiltration by Gaucher cells and hypersplenism. However, some cases of cytopenia in splenectomized or treated patients suggest possible other mechanisms. To evaluate intra\u2010cellular glucocerebrosidase (GlcC) activity in immature progenitors and to prove the conduritol B epoxide (CBE)\u2010induced inhibition of the enzyme, we used an adapted flow cytometric technique before assessing the direct effect of GlcC deficiency in functional assays. Among haematopoietic cells from healthy donors, monocytes showed the highest GlcC activity but immature CD34<jats:sup>+<\/jats:sup> and mesenchymal cells also had significant GlcC activity. CBE greatly inhibited the enzyme activity of all cell categories. GlcC\u2010deficient CD34<jats:sup>+<\/jats:sup> cells showed impaired ability to proliferate and differentiate in the expansion assay and had lower frequency of erythroid burst\u2010forming units, granulocyte colony\u2010forming units (CFU) and macrophage CFU progenitors, but the effect of GlcC deficiency on megakaryocyte CFU lineage was not significant. GlcC deficiency strongly impaired primitive haematopoiesis in long\u2010term culture. Furthermore, GlcC deficiency progressively impaired proliferation of mesenchymal progenitors. These data suggest an intrinsic effect of GlcC deficiency on BM immature cells that supplements the pathophysiology of GD and opens new perspectives of therapeutic approach.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2010.08214.x","type":"journal-article","created":{"date-parts":[[2010,5,10]],"date-time":"2010-05-10T00:56:09Z","timestamp":1273452969000},"page":"93-101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Glucocerebrosidase deficiency dramatically impairs human bone marrow haematopoiesis in an <i>in vitro<\/i> model of Gaucher disease"],"prefix":"10.1111","volume":"150","author":[{"given":"Juliette","family":"Berger","sequence":"first","affiliation":[]},{"given":"S\u00e9verine","family":"Lecourt","sequence":"additional","affiliation":[]},{"given":"Val\u00e9rie","family":"Vanneaux","sequence":"additional","affiliation":[]},{"given":"Chantal","family":"Rapatel","sequence":"additional","affiliation":[]},{"given":"St\u00e9phane","family":"Boisgard","sequence":"additional","affiliation":[]},{"given":"Catherine","family":"Caillaud","sequence":"additional","affiliation":[]},{"given":"Nathalie","family":"Boiret\u2010Dupr\u00e9","sequence":"additional","affiliation":[]},{"given":"Christine","family":"Chomienne","sequence":"additional","affiliation":[]},{"given":"Jean\u2010Pierre","family":"Marolleau","sequence":"additional","affiliation":[]},{"given":"J\u00e9r\u00f4me","family":"Larghero","sequence":"additional","affiliation":[]},{"given":"Marc G.","family":"Berger","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2010,6,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/90.1.19"},{"key":"e_1_2_6_3_1","first-page":"205","article-title":"Cytokines in Gaucher\u2019s disease","volume":"10","author":"Barak V.","year":"1999","journal-title":"European Cytokine Network"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(70)91646-6"},{"key":"e_1_2_6_5_1","first-page":"747","article-title":"The diagnosis of the adult type of Gaucher\u2019s disease and its carrier state by demonstration of deficiency of beta\u2010glucosidase activity in peripheral blood leukocytes","volume":"76","author":"Beutler E.","year":"1970","journal-title":"Journal of Laboratory and Clinical Medicine"},{"key":"e_1_2_6_6_1","first-page":"1762","volume-title":"Hematology","author":"Beutler E.","year":"1990"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2003.08.010"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2007.04.002"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-205708"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1986.tb09417.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(87)90019-X"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2005.05.005"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005454602454"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61522-6"},{"key":"e_1_2_6_15_1","first-page":"1","volume-title":"The online metabolic & molecular bases of inherited disease","author":"Grabowski G.A.","year":"2006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800092-JLR200"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05351.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300212200"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.9.3412"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020267831851"},{"key":"e_1_2_6_21_1","first-page":"201","article-title":"Transduction of mobilized peripheral blood CD34+ cells with the glucocerebrosidase cDNA","volume":"1","author":"Nimgaonkar M.T.","year":"1994","journal-title":"Gene Therapy"},{"issue":"1","key":"e_1_2_6_22_1","first-page":"S38","article-title":"Long\u2010term expression of the glucocerebrosidase gene in mouse and human hematopoietic progenitors","volume":"9","author":"Nimgaonkar M.","year":"1995","journal-title":"Leukemia"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801990200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2004.07.009"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(76)90547-6"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.9.3584"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.1.1996.5.213"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(91)90066-I"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06786.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01150-6"},{"key":"e_1_2_6_31_1","first-page":"416","article-title":"Gaucher\u2010like changes in human blood\u2010derived macrophages induced by beta\u2010glucocerebrosidase inhibition","volume":"111","author":"Yatziv S.","year":"1988","journal-title":"Journal of Laboratory and Clinical Medicine"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-200X.2007.02502.x"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2141.2010.08214.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2141.2010.08214.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T02:47:03Z","timestamp":1697424423000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2141.2010.08214.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,9]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,7]]}},"alternative-id":["10.1111\/j.1365-2141.2010.08214.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2141.2010.08214.x","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,9]]},"assertion":[{"value":"2010-06-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}