Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis
Acute Myeloid Leukemia is one of the most aggressive blood cancers with a high frequency of relapse. While standard chemotherapy is able to target rapidly proliferating immature blasts, it fails to eradicate slowly proliferating Leukemic Stem Cells. Therefore, new therapeutic strategies that efficie...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Springer Nature
2022-07-01
|
Series: | EMBO Molecular Medicine |
Online Access: | https://doi.org/10.15252/emmm.202216171 |
_version_ | 1797282668173328384 |
---|---|
author | Elisa Donato Andreas Trumpp |
author_facet | Elisa Donato Andreas Trumpp |
author_sort | Elisa Donato |
collection | DOAJ |
description | Acute Myeloid Leukemia is one of the most aggressive blood cancers with a high frequency of relapse. While standard chemotherapy is able to target rapidly proliferating immature blasts, it fails to eradicate slowly proliferating Leukemic Stem Cells. Therefore, new therapeutic strategies that efficiently target LSCs are urgently needed. Recent studies suggest that LSCs have particular metabolic vulnerabilities, which would open the possibility of a therapeutic window with limited off‐target effects on the normal hematopoietic system. In this issue of EMBO Molecular Medicine, So and colleagues investigate the mechanism of action of AG636, a new potent inhibitor of de novo pyrimidine synthesis, and discovered an unexpected link to AML protein translation essential for LSC function. |
first_indexed | 2024-03-07T17:16:24Z |
format | Article |
id | doaj.art-fd8a9c2bbc764bf9b637ed0ba987c60f |
institution | Directory Open Access Journal |
issn | 1757-4676 1757-4684 |
language | English |
last_indexed | 2024-03-07T17:16:24Z |
publishDate | 2022-07-01 |
publisher | Springer Nature |
record_format | Article |
series | EMBO Molecular Medicine |
spelling | doaj.art-fd8a9c2bbc764bf9b637ed0ba987c60f2024-03-02T22:27:52ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-07-01147n/an/a10.15252/emmm.202216171Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesisElisa Donato0Andreas Trumpp1Division of Stem Cells and Cancer German Cancer Research Center (DKFZ) and DKFZ‐ZMBH Alliance Heidelberg GermanyDivision of Stem Cells and Cancer German Cancer Research Center (DKFZ) and DKFZ‐ZMBH Alliance Heidelberg GermanyAcute Myeloid Leukemia is one of the most aggressive blood cancers with a high frequency of relapse. While standard chemotherapy is able to target rapidly proliferating immature blasts, it fails to eradicate slowly proliferating Leukemic Stem Cells. Therefore, new therapeutic strategies that efficiently target LSCs are urgently needed. Recent studies suggest that LSCs have particular metabolic vulnerabilities, which would open the possibility of a therapeutic window with limited off‐target effects on the normal hematopoietic system. In this issue of EMBO Molecular Medicine, So and colleagues investigate the mechanism of action of AG636, a new potent inhibitor of de novo pyrimidine synthesis, and discovered an unexpected link to AML protein translation essential for LSC function.https://doi.org/10.15252/emmm.202216171 |
spellingShingle | Elisa Donato Andreas Trumpp Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis EMBO Molecular Medicine |
title | Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis |
title_full | Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis |
title_fullStr | Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis |
title_full_unstemmed | Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis |
title_short | Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis |
title_sort | targeting the leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis |
url | https://doi.org/10.15252/emmm.202216171 |
work_keys_str_mv | AT elisadonato targetingtheleukemicstemcellproteinmachinerybyinhibitionofmitochondrialpyrimidinesynthesis AT andreastrumpp targetingtheleukemicstemcellproteinmachinerybyinhibitionofmitochondrialpyrimidinesynthesis |