Novel biomarker for diagnosis and targeted therapy of Acute Myeloid Leukemia (AML)
Medicine : Diagnostics
Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. Mutations and cytogenetic aberrations are used to stratify patients into prognostic subgroups and specify drug treatment. However, even though genomics has helped to resolve some of the clinical heterogeneity of AML and revealed specific drug targets, there continues to be a mismatch between genomic risk stratification and clinical outcome for some individual patients. Identification of novel clinically relevant biomarkers is vital in order to improve prognostic classification, risk assessment and therapeutic decision-making in AML.
Scientists from the Max-Planck-Institute of Biochemistry have performed a comprehensive proteogenomic analysis of bone-marrow biopsies from 252 uniformly treated patients with AML and were able to identify one subtype (Mito-AML) which was characterized by high expression of mitochondrial proteins and showed poor outcome, with reduced remission rate and shorter overall survival upon treatment with intensive induction chemotherapy. Functional analyses revealed that Mito-AML is metabolically wired towards stronger complex I-dependent respiration and is hyperresponsive to the inhibitors mubritinib, venetoclax and to combined venetoclax/azacitidine treatment, all of which target mitochondrial respiration. Therefore, proteomic signatures defining Mito-AML represent ideal biomarker candidates for diagnostic sub-classification of AML patients with elevated expression of mitochondrial proteins and subsequent targeted therapy with BCL-2 inhibitors like venetoclax and/or agents targeting mitochondrial complex I.
We are now looking for either a licensing partner, or a collaboration partner to further develop this project.
Jayavelu et al., 2022. Cancer Cell. DOI: 10.1016/j.ccell.2022.02.006
A patent application was filed on December, 22nd 2021.
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Dr. Mareike Göritz
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