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In leukaemia, the balance of B\u2010cell lymphoma\u20102 (BCL\u20102) family proteins is disrupted, promoting survival of malignant cells and possibly LPC. A direct comparison of BCL\u20102 inhibitors, navitoclax and venetoclax, was undertaken on LPC subpopulations from B\u2010cell precursor (BCP) and T\u2010cell ALL (T\u2010ALL) cases <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Responses were compared to BCL\u20102 levels detected by microarray analyses and Western blotting. <jats:italic>In vitro<\/jats:italic>, both drugs were effective against most BCP\u2010ALL LPC, except CD34<jats:sup>\u2212<\/jats:sup>\/CD19<jats:sup>\u2212<\/jats:sup> cells. In contrast, only navitoclax was effective in T\u2010ALL and CD34<jats:sup>\u2212<\/jats:sup>\/CD7<jats:sup>\u2212<\/jats:sup> LPC were resistant to both drugs. <jats:italic>In vivo<\/jats:italic>, navitoclax was more effective than venetoclax, significantly improving survival of mice engrafted with BCP\u2010 and T\u2010ALL samples. Venetoclax was not particularly effective against T\u2010ALL cases <jats:italic>in vivo<\/jats:italic>. The proportions of CD34<jats:sup>+<\/jats:sup>\/CD19<jats:sup>\u2212<\/jats:sup>, CD34<jats:sup>\u2212<\/jats:sup>\/CD19<jats:sup>\u2212<\/jats:sup> BCP\u2010ALL cells and CD34<jats:sup>\u2212<\/jats:sup>\/CD7<jats:sup>\u2212<\/jats:sup> T\u2010ALL cells increased significantly following <jats:italic>in vivo<\/jats:italic> treatment. Expression of pro\u2010apoptotic BCL\u20102 genes was lower in these subpopulations, which may explain the lack of sensitivity. These data demonstrate that some LPC were resistant to BCL\u20102 inhibitors and sustained remission will require their use in combination with other therapeutics.<\/jats:p>","DOI":"10.1111\/bjh.16773","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T05:21:20Z","timestamp":1590470480000},"page":"577-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating the response of paediatric leukaemia\u2010propagating cells to BCL\u20102 inhibitors"],"prefix":"10.1111","volume":"192","author":[{"given":"Paraskevi","family":"Diamanti","sequence":"first","affiliation":[{"name":"Bristol Institute for Transfusion Sciences NHSBT Filton Bristol UK"},{"name":"School of Cellular and Molecular Medicine University of Bristol Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin C.","family":"Ede","sequence":"additional","affiliation":[{"name":"School of 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