Thursday, February 7, 2013
This week in
B cell lymphoma 2
Mouse and cell culture
studies suggest BCL-2 inhibitors could be useful for selectively killing
leukemia stem cells. In mice engrafted with human chronic myelogenous
leukemia (CML) stem cells, the pan-BCL-2 inhibitor sabutoclax
decreased stem cell burden and increased stem cell sensitivity to the
tyrosine kinase inhibitor Sprycel dasatinib compared with
vehicle. In CML stem cell-enriched primary acute myelogenous leukemia (AML)
samples, compared with non-stem cell-enriched AML samples, two related BCL-2
inhibitors, ABT-263 and ABT-737,
caused selective increases in cell death. Next steps could include a clinical
trial of BCL-2 inhibitors in combination with other antileukemia therapies.
Squibb Co. markets Sprycel to treat acute lymphoblastic
leukemia (ALL) and CML.
Laboratories and Roche's
Inc. unit have ABT-263 in Phase I/II testing or earlier to
treat various cancers. ABT-737 is a research reagent from Abbott.
Inc.'s sabutoclax is in preclinical development to treat
At least seven other companies have BCL-2 inhibitors in Phase II testing to
treat various cancers including leukemia and lymphoma.
Published online Feb. 7, 2013
Patent and licensing status
Goff, D.J. et al. Cell
Stem Cell; published online Jan. 17, 2013;
Contact: Catriona H.M. Jamieson, University of California,
San Diego, La Jolla, Calif.
Lagadinou, E.D. et al. Cell Stem Cell; published online Jan. 17, 2013;
Contact: Craig T. Jordan, University of Rochester Medical
Center, Rochester, N.Y.
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