{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T17:52:44Z","timestamp":1757699564228,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,25]],"date-time":"2018-11-25T00:00:00Z","timestamp":1543104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Doelfonds Leukemie van de Bontius Stichting"},{"name":"Frank Sanderse Stichting"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adult B\u2010lymphoblastic leukemia (B\u2010ALL) is a hematological malignancy characterized by genetic heterogeneity. Despite successful remission induction with classical chemotherapeutics and novel targeted agents, enduring remission is often hampered by disease relapse due to outgrowth of a pre\u2010existing subclone resistant against the treatment. In this study, we show that small glycophosphatidylinositol (GPI)\u2010anchor deficient CD52\u2010negative B\u2010cell populations are frequently present already at diagnosis in B\u2010ALL patients, but not in patients suffering from other B\u2010cell malignancies. We demonstrate that the GPI\u2010anchor negative phenotype results from loss of mRNA expression of the <jats:italic>PIGH<\/jats:italic> gene, which is involved in the first step of GPI\u2010anchor synthesis. Loss of <jats:italic>PIGH<\/jats:italic> mRNA expression within these B\u2010ALL cells follows epigenetic silencing rather than gene mutation or deletion. The coinciding loss of CD52 membrane expression may contribute to the development of resistance to alemtuzumab (ALM) treatment in B\u2010ALL patients resulting in the outgrowth of CD52\u2010negative escape variants. Additional treatment with 5\u2010aza\u20102\u2032\u2010deoxycytidine may restore expression of CD52 and revert ALM resistance.<\/jats:p>","DOI":"10.1002\/ajh.25337","type":"journal-article","created":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T12:30:34Z","timestamp":1540816234000},"page":"93-102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Loss of the GPI\u2010anchor in B\u2010lymphoblastic leukemia by epigenetic downregulation of <i>PIGH<\/i> expression"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7059-2038","authenticated-orcid":false,"given":"Floris C.","family":"Loeff","sequence":"first","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Rijs","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther H. M.","family":"van Egmond","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem H.","family":"Zoutman","sequence":"additional","affiliation":[{"name":"Department of Dermatology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Division of Cell Biology The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilhelmina G. M.","family":"Kroes","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina A. J.","family":"Veld","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke","family":"Griffioen","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten H.","family":"Vermeer","sequence":"additional","affiliation":[{"name":"Department of Dermatology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Neefjes","sequence":"additional","affiliation":[{"name":"Division of Cell Biology The Netherlands Cancer Institute  Amsterdam The Netherlands"},{"name":"Department of Chemical Immunology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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