Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023473 (
chronic myeloid leukemia
)
18,916
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Adipose tissue (AT) has previously been identified as an extra-medullary reservoir for normal hematopoietic stem cells (HSCs) and may promote tumor development. Here, we show that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis
chronic myeloid leukemia
(
CML
), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT. GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the fatty acid transporter
CD36
.
CD36
(+) LSCs have unique metabolic properties, are strikingly enriched in AT, and are protected from chemotherapy by the GAT microenvironment.
CD36
also marks a fraction of human blast crisis
CML
and acute myeloid leukemia (AML) cells with similar biological properties. These findings suggest striking interplay between leukemic cells and AT to create a unique microenvironment that supports the metabolic demands and survival of a distinct LSC subpopulation.
...
PMID:Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche. 2739 17
Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of
chronic myeloid leukemia
(
CML
), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34
+
CD38
low
) and progenitor (CD34
+
CD38
+
) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive
CML
cells, we confirmed upregulation of the scavenger receptor
CD36
and the leptin receptor by flow cytometry. We also delineate a subpopulation of primitive
CML
cells expressing
CD36
that is less sensitive to imatinib treatment. Using
CD36
targeting antibodies, we show that the
CD36
positive cells can be targeted and killed by antibody-dependent cellular cytotoxicity. In summary,
CD36
defines a subpopulation of primitive
CML
cells with decreased imatinib sensitivity that can be effectively targeted and killed using an anti-
CD36
antibody.
...
PMID:CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting. 2928 80
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