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Treatment options for hypereosinophilia remain limited despite recent approaches including IL-5-targeted monoclonal antibodies and tyrosine kinase inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To understand aberrant survival patterns and options for pharmacologic intervention, we characterized BCL-2-regulated apoptosis signaling by testing for BCL-2 family expression levels as well as pharmacologic inhibition using primary patient samples from diverse subtypes of hypereosinophilia (hypereosinophilic syndrome<jats:italic>n<\/jats:italic>\u2009=\u200918, chronic eosinophilic leukemia not otherwise specified<jats:italic>n<\/jats:italic>\u2009=\u20099, lymphocyte-variant hypereosinophilia<jats:italic>n<\/jats:italic>\u2009=\u20092, myeloproliferative neoplasm with eosinophilia<jats:italic>n<\/jats:italic>\u2009=\u20092, eosinophilic granulomatosis with polyangiitis<jats:italic>n<\/jats:italic>\u2009=\u200911, reactive eosinophilia<jats:italic>n<\/jats:italic>\u2009=\u20093).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Contrary to published literature, we found no difference in the levels of the lncRNA<jats:italic>Morrbid<\/jats:italic>and its target<jats:italic>BIM<\/jats:italic>. Yet, we identified a near complete loss of expression of pro-apoptotic<jats:italic>PUMA<\/jats:italic>as well as a reduction in anti-apoptotic<jats:italic>BCL-2<\/jats:italic>. Accordingly,<jats:italic>BCL-2<\/jats:italic>inhibition using venetoclax failed to achieve cell death induction in eosinophil granulocytes and bone marrow mononuclear cells from patients with hypereosinophilia. In contrast,<jats:italic>MCL1<\/jats:italic>inhibition using S63845 specifically decreased the viability of bone marrow progenitor cells in patients with hypereosinophilia. In patients diagnosed with Chronic Eosinophilic Leukemia (CEL-NOS) or Myeloid and Lymphatic Neoplasia with hypereosinophilia (MLN-Eo) repression of survival was specifically powerful.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study shows that<jats:italic>MCL1<\/jats:italic>inhibition might be a promising therapeutic option for hypereosinophilia patients specifically for CEL-NOS and MLN-Eo.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00432-021-03827-9","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T19:44:00Z","timestamp":1634327040000},"page":"331-340","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive characterization of central BCL-2 family members in aberrant eosinophils and their impact on therapeutic strategies"],"prefix":"10.1007","volume":"148","author":[{"given":"Timo O.","family":"Odinius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Buschhorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celina","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T.","family":"Hauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Dill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Dechant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele C.","family":"Buck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Shoumariyeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Moog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Schwaab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Brockow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"G\u00f6tze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Bassermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"H\u00f6ckendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Branca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp J.","family":"Jost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1774-7605","authenticated-orcid":false,"given":"Stefanie","family":"Jilg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"3827_CR1","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1038\/s41388-020-1212-9","volume":"39","author":"M Bessou","year":"2020","unstructured":"Bessou M et al (2020) The apoptosis inhibitor Bcl-xL controls breast cancer cell migration through mitochondria-dependent reactive oxygen species production. 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All investigations were approved by the Local Ethics Committee of the School of Medicine of the Technical University of Munich (Project 62\/16S).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}]}}