Open AccessClearance of systemic hematologic tumors by venetoclax (Abt‐199) and navitoclax
Author(s) -
Ackler Scott,
Oleksijew Anatol,
Chen Jun,
Chyla Brenda J.,
Clarin Jerry,
Foster Kelly,
McGonigal Thomas,
Mishra Sasmita,
Schlessinger Sally,
Smith Morey L.,
Tahir Stephen K.,
Leverson Joel D.,
Souers Andrew J.,
Boghaert Erwin R.,
Hickson Jonathan
Publication year - 2015
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.178
Subject(s) - venetoclax , medicine , bone marrow , cancer research , lymphoma , mantle cell lymphoma , chronic lymphocytic leukemia , leukemia , multiple myeloma , immunology
The Bcl‐2 family inhibitors venetoclax and navitoclax demonstrated potent antitumor activity in chronic lymphocytic leukemia patients, notably in reducing marrow load and adenopathy. Subsequent trials with venetoclax have been initiated in non‐Hodgkin's lymphoma and multiple myeloma patients. Traditional preclinical models fall short either in faithfully recapitulating disease progression within such compartments or in allowing the direct longitudinal analysis of systemic disease. We show that intravenous inoculation of engineered RS4;11 (acute lymphoblastic leukemia) and Granta 519 (mantle cell lymphoma) bioluminescent reporter cell lines result in tumor engraftment of bone marrow, with additional invasion of the central nervous system in the case of Granta 519. Importantly, apoptosis induction and response of these systemically engrafted tumors to Bcl‐2 family inhibitors alone or in combination with standard‐of‐care agents could be monitored longitudinally with optical imaging, and was more accurately reflective of the observed clinical response.