{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:55:54Z","timestamp":1791093354405,"version":"4.1.0"},"reference-count":49,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,1,12]]},"abstract":"<jats:p>The characterization and targeting of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL)\u2013initiating cells remains unresolved. Expression of the polycomb protein Bmi1 is up-regulated in patients with advanced stages of chronic myelogenous leukemia (CML). We report that Bmi1 transforms and reprograms CML B-lymphoid progenitors into stem cell leukemia (Scl) promoter-driven, self-renewing, leukemia-initiating cells to result in B-lymphoid leukemia (B-ALL) in vivo. In vitro, highly proliferating and serially replatable myeloid and lymphoid colony-forming cultures could be established from BCR-ABL and Bmi1 coexpressing progenitors. However, unlike in vivo expanded CML B-lymphoid progenitors, hematopoietic stem cells, or multipotent progenitors, coexpressing BCR-ABL and Bmi1 did not initiate or propagate leukemia in a limiting dilution assay. Inducible genetic attenuation of BCR-ABL reversed Bmi1-driven B-ALL development, which was accompanied by induction of apoptosis of leukemic B-lymphoid progenitors and by long-term animal survival, suggesting that BCR-ABL is required to maintain B-ALL and that BCR-ABL and Bmi1 cooperate toward blast transformation in vivo. Our data indicate that BCR-ABL targeting itself is required to eradicate Ph+\/Bmi1+ B-ALL\u2013initiating cells and confirm their addiction to BCR-ABL signaling.<\/jats:p>","DOI":"10.1182\/blood-2011-06-359232","type":"journal-article","created":{"date-parts":[[2011,11,19]],"date-time":"2011-11-19T00:29:33Z","timestamp":1321662573000},"page":"494-502","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":30,"title":["Bmi1 reprograms CML B-lymphoid progenitors to become B-ALL\u2013initiating cells"],"prefix":"10.1182","volume":"119","author":[{"given":"Amitava","family":"Sengupta","sequence":"first","affiliation":[{"name":"Stem Cell Program, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH;"},{"name":"Structural Genomics Division, Saha Institute of Nuclear Physics, West Bengal, India; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley 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