{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:35:59Z","timestamp":1791326159824,"version":"4.3.1"},"reference-count":152,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Clinical progression of B cell chronic lymphocytic leukemia (B-CLL) reflects the clone\u2019s Ag receptor (BCR) and involves stroma-dependent B-CLL growth within lymphoid tissue. Uniformly elevated expression of TLR-9, occasional MYD88 mutations, and BCR specificity for DNA or Ags physically linked to DNA together suggest that TLR-9 signaling is important in driving B-CLL growth in patients. Nevertheless, reports of apoptosis after B-CLL exposure to CpG oligodeoxynucleotide (ODN) raised questions about a central role for TLR-9. Because normal memory B cells proliferate vigorously to ODN+IL-15, a cytokine found in stromal cells of bone marrow, lymph nodes, and spleen, we examined whether this was true for B-CLL cells. Through a CFSE-based assay for quantitatively monitoring in vitro clonal proliferation\/survival, we show that IL-15 precludes TLR-9\u2013induced apoptosis and permits significant B-CLL clonal expansion regardless of the clone\u2019s BCR mutation status. A robust response to ODN+IL-15 was positively linked to presence of chromosomal anomalies (trisomy-12 or ataxia telangiectasia mutated anomaly + del13q14) and negatively linked to a very high proportion of CD38+ cells within the blood-derived B-CLL population. Furthermore, a clone\u2019s intrinsic potential for in vitro growth correlated directly with doubling time in blood, in the case of B-CLL with Ig H chain V region\u2013unmutated BCR and &amp;lt;30% CD38+ cells in blood. Finally, in vitro high-proliferator status was statistically linked to diminished patient survival. These findings, together with immunohistochemical evidence of apoptotic cells and IL-15\u2013producing cells proximal to B-CLL pseudofollicles in patient spleens, suggest that collaborative ODN and IL-15 signaling may promote in vivo B-CLL growth.<\/jats:p>","DOI":"10.4049\/jimmunol.1403189","type":"journal-article","created":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T01:00:54Z","timestamp":1435798854000},"page":"901-923","source":"Crossref","is-referenced-by-count":62,"title":["TLR-9 and IL-15 Synergy Promotes the In Vitro Clonal Expansion of Chronic Lymphocytic Leukemia B Cells"],"prefix":"10.1093","volume":"195","author":[{"given":"Patricia K A","family":"Mongini","sequence":"first","affiliation":[{"name":"The Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health System , Manhasset, NY 11030"},{"name":"Department of Molecular Medicine, Hofstra North Shore\u2013LIJ School of Medicine , Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Gupta","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health System , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Boyle","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health System , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Nieto","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health System , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjoo","family":"Lee","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health 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Hempstead, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanti","family":"Rai","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health System , Manhasset, NY 11030"},{"name":"Department of Medicine, North Shore University Hospital\u2013Long Island Jewish Medical Center , Manhasset, NY"},{"name":"Department of Medicine, Hofstra North Shore\u2013LIJ School of Medicine , Hempstead, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C","family":"Chu","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, North Shore\u2013Long Island Jewish Health System , Manhasset, NY 11030"},{"name":"Department of Molecular Medicine, Hofstra North Shore\u2013LIJ School of Medicine , Hempstead, NY 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