Targeting the Mitochondrial Processing Peptidase as a Therapeutic Strategy for Acute Myeloid Leukemia
Year: 2014
Type: dissertation
Abstract: Acute myeloid leukemia (AML) is a highly heterogeneous disease characterized by a wide variety of cytogenetic abnormalities. Treatment has been largely unchanged for the past two decades and prognosis is still poor; thus, new therapeutics is needed for this disease. Here, we explore the possibility of targeting the Mitochondrial Processing Peptidase (MPP) as a potential therapeutic target for AML. MPP is a heterodimeric zinc metallopeptidase that cleaves presequences following the import of nuclear encoded matrix space precursors. We demonstrate that MPP-α is overexpressed in a subset of AML patient blood and stem/progenitor populations. MPP-α is ubiquitously expressed in human tissues and strongly expressed in heart and brain. Furthermore, AML cell lines are differentially susceptible towards genetic knockdown of MPP-α with OCI-AML2 having the greatest decrease in cell viability and proliferation while K562 and TEX have moderate effects. These results warrant further investigation of MPP as a therapeutic target for AML.
Source: TSpace (University of Toronto)
Author: Ashwin Ramakrishnan
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2751412980