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SMS121, a new inhibitor of CD36, impairs fatty acid uptake and viability of acute myeloid leukemia

Åbacka, Hannah LU orcid ; Masoni, Samuele LU ; Poli, Giulio ; Huang, Peng LU ; Gusso, Francesco ; Granchi, Carlotta ; Minutolo, Filippo ; Tuccinardi, Tiziano ; Hagström-Andersson, Anna K. LU orcid and Lindkvist-Petersson, Karin LU (2024) In Scientific Reports 14(1).
Abstract

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival. Here we show that fatty acids are transferred from human primary adipocytes to AML cells upon... (More)

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival. Here we show that fatty acids are transferred from human primary adipocytes to AML cells upon co-culturing. A drug-like small molecule (SMS121) was identified by receptor-based virtual screening and experimentally demonstrated to target the lipid uptake protein CD36. SMS121 reduced the uptake of fatty acid into AML cells that could be reversed by addition of free fatty acids and caused decreased cell viability. The data presented here serves as a framework for the development of CD36 inhibitors to be used as future therapeutics against AML.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute myeloid leukemia, Adipocyte, AML, CD36, Fatty acid
in
Scientific Reports
volume
14
issue
1
article number
9104
publisher
Nature Publishing Group
external identifiers
  • pmid:38643249
  • scopus:85190774254
ISSN
2045-2322
DOI
10.1038/s41598-024-58689-1
language
English
LU publication?
yes
id
9b275b74-67e5-4d15-bc35-326f6579143a
date added to LUP
2025-01-08 10:50:14
date last changed
2025-07-10 15:24:01
@article{9b275b74-67e5-4d15-bc35-326f6579143a,
  abstract     = {{<p>Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival. Here we show that fatty acids are transferred from human primary adipocytes to AML cells upon co-culturing. A drug-like small molecule (SMS121) was identified by receptor-based virtual screening and experimentally demonstrated to target the lipid uptake protein CD36. SMS121 reduced the uptake of fatty acid into AML cells that could be reversed by addition of free fatty acids and caused decreased cell viability. The data presented here serves as a framework for the development of CD36 inhibitors to be used as future therapeutics against AML.</p>}},
  author       = {{Åbacka, Hannah and Masoni, Samuele and Poli, Giulio and Huang, Peng and Gusso, Francesco and Granchi, Carlotta and Minutolo, Filippo and Tuccinardi, Tiziano and Hagström-Andersson, Anna K. and Lindkvist-Petersson, Karin}},
  issn         = {{2045-2322}},
  keywords     = {{Acute myeloid leukemia; Adipocyte; AML; CD36; Fatty acid}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{SMS121, a new inhibitor of CD36, impairs fatty acid uptake and viability of acute myeloid leukemia}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-58689-1}},
  doi          = {{10.1038/s41598-024-58689-1}},
  volume       = {{14}},
  year         = {{2024}},
}