2010
DOI: 10.1124/mol.109.060780
|View full text |Cite
|
Sign up to set email alerts
|

The Bcl-2 Homology Domain 3 Mimetic ABT-737 Targets the Apoptotic Machinery in Acute Lymphoblastic Leukemia Resulting in Synergistic in Vitro and in Vivo Interactions with Established Drugs

Abstract: Antiapoptotic Bcl-2 proteins are overexpressed in a number of cancers, including leukemias, and are frequently associated with resistance to conventional chemotherapeutic drugs. ABT-737, a Bcl-2 homology domain 3 mimetic (for structure, see Nature 435: [677][678][679][680][681] 2005) inhibits the prosurvival function of Bcl-2, Bcl-X L , and Bcl-w. We show that ABT-737 was effective as a single agent against a panel of pediatric acute lymphoblastic leukemia (ALL) xenografts, previously established, from patien… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

5
99
1
1

Year Published

2010
2010
2023
2023

Publication Types

Select...
8
1

Relationship

0
9

Authors

Journals

citations
Cited by 111 publications
(106 citation statements)
references
References 42 publications
5
99
1
1
Order By: Relevance
“…97 Certain Bcl-2 inhibitors (Abt-737) may sensitize chronic lymphocytic leukemia and chronic myeloid leukemia cells to chemotherapy, implicating Bcl-2 family members that are sensitive to Abl-737 (for example, Bcl-2 and Bcl-XL, but not Mcl-1) in their drug resistance. 98,99 Bcl-2 inhibitors sensitize B lymphoma cells to rituximab, a chimeric monoclonal antibody that targets CD20 (ref. 100).…”
Section: Targeting Translation Governed By Pi3k Pathway Am Martelli Ementioning
confidence: 99%
“…97 Certain Bcl-2 inhibitors (Abt-737) may sensitize chronic lymphocytic leukemia and chronic myeloid leukemia cells to chemotherapy, implicating Bcl-2 family members that are sensitive to Abl-737 (for example, Bcl-2 and Bcl-XL, but not Mcl-1) in their drug resistance. 98,99 Bcl-2 inhibitors sensitize B lymphoma cells to rituximab, a chimeric monoclonal antibody that targets CD20 (ref. 100).…”
Section: Targeting Translation Governed By Pi3k Pathway Am Martelli Ementioning
confidence: 99%
“…[90][91][92][93] Certain Bcl-2 inhibitors (for example, Abt-737) may sensitize chronic lymphocytic leukemia and chronic myeloid leukemia cells to chemotherapy, implicating the Bcl-2 family members, which are sensitive to Abl-737 (for example, Bcl-2 and Bcl-X L but not Mcl-1) in their drug resistance. [94][95] Bcl-2 inhibitors sensitize B lymphoma cells to rituximab, a chimeric monoclonal antibody, which targets CD20. 96 Bcl-2 inhibitors also render various lymphoid malignancies susceptible to proteasome inhibitors.…”
Section: Flt3 Mutations and Leukemia Therapymentioning
confidence: 99%
“…We have observed potent antileukemic single-agent activity using the currently best-characterized small-molecule BH3 mimetic, ABT-737 [19], and its orally available derivative, ABT-263 [8, [20][21][22].…”
Section: Improved Preclinal Modeling Of Drug-resistant Diseasementioning
confidence: 99%
“…In vivo, using xenograft models, ABT-737 potentiated the effect of a three-drug regimen, with dexamethasone, l-asparaginase and vincristine [25], and delayed leukemia progression in combination with l -asparaginase, topotecan, vincristine or etoposide [21]. Provided reliable predictive markers can be established to select patients that will respond to this drug, addition of ABT-263 to a multidrug regimen with a second-line chemotherapy agent should be investigated with priority.…”
Section: Improved Preclinal Modeling Of Drug-resistant Diseasementioning
confidence: 99%