자료유형  

 학위논문

Control Number  

0016934984

International Standard Book Number  

9798380170123

Dewey Decimal Classification Number  

616.99

Main Entry-Personal Name  

Rinella, Sean.

Publication, Distribution, etc. (Imprint  

[S.l.] : The University of Wisconsin - Madison., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(106 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

General Note  

Advisor: Capitini, Christian M.

Dissertation Note  

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Treatment of relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) remains a challenge, particularly in patients who do not respond to traditional chemotherapy or immunotherapy. The objective of this study was to assess the efficacy of fedratinib, a semi selective JAK2 inhibitor and venetoclax, a selective BCL-2 inhibitor, on human B-ALL using both single-agent and combinatorial treatments. The combination treatment of fedratinib and venetoclax improved killing of the human B-ALL cell lines RS4;11 and SUP-B15 in vitro over single-agent treatments. This combinatorial effect was not detected in the human B-ALL cell line NALM-6, which was less responsive to fedratinib due to the absence of FLT3 expression. The combination treatment induces a unique gene expression profile relative to single-agent treatment and with an enrichment in apoptotic pathways. Finally, the combination treatment was superior to single agent treatment in an in vivo xenograft model of human B-ALL with a two-week treatment regimen significantly improving overall survival. Overall, our data demonstrates the efficacy of a combinatorial treatment strategy of fedratinib and venetoclax against human B-ALL expressing high levels of FLT3.

Subject Added Entry-Topical Term  

Oncology.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Clinical psychology.

Index Term-Uncontrolled  

Hematology

Index Term-Uncontrolled  

Leukemia

Index Term-Uncontrolled  

Pediatrics

Index Term-Uncontrolled  

Immunotherapy

Index Term-Uncontrolled  

Venetoclax

Added Entry-Corporate Name  

The University of Wisconsin - Madison Clinical Investigation - MED

Host Item Entry  

Dissertations Abstracts International. 85-03B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643414