Aberrant Bone Homeostasis in AML Is Associated with Activated Oncogenic FLT3-Dependent Cytokine Networks.
Animals
Bone and Bones
/ pathology
Cell Line, Tumor
Cytokines
/ metabolism
Gene Duplication
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Hematopoietic Stem Cells
/ metabolism
Homeostasis
Humans
Leukemia, Myeloid, Acute
/ genetics
Mice
Oncogenes
Osteoblasts
/ metabolism
Osteoclasts
/ metabolism
Osteogenesis
Prognosis
RAW 264.7 Cells
Signal Transduction
fms-Like Tyrosine Kinase 3
/ genetics
FMS-like tyrosine kinase 3 (FLT3)
acute myeloid leukaemia (AML)
bone remodelling
haematopoiesis
haematopoietic niche
osteoblast (OB)
osteoblastogenesis
osteoclast (OC)
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
09 11 2020
09 11 2020
Historique:
received:
05
10
2020
revised:
04
11
2020
accepted:
05
11
2020
entrez:
13
11
2020
pubmed:
14
11
2020
medline:
17
6
2021
Statut:
epublish
Résumé
Acute myeloid leukaemia (AML) is a haematopoietic malignancy caused by a combination of genetic and epigenetic lesions. Activation of the oncoprotein FLT3 ITD (Fms-like tyrosine kinase with internal tandem duplications) represents a key driver mutation in 25-30% of AML patients. FLT3 is a class III receptor tyrosine kinase, which plays a role in cell survival, proliferation, and differentiation of haematopoietic progenitors of lymphoid and myeloid lineages. Mutant FLT3 ITD results in an altered signalling quality, which causes cell transformation. Recent evidence indicates an effect of FLT3 ITD on bone homeostasis in addition to haematological aberrations. Using gene expression data repositories of FLT3 ITD-positive AML patients, we identified activated cytokine networks that affect the formation of the haematopoietic niche by controlling osteoclastogenesis and osteoblast functions. In addition, aberrant oncogenic FLT3 signalling of osteogenesis-specific cytokines affects survival of AML patients and may be used for prognosis. Thus, these data highlight the intimate crosstalk between leukaemic and osteogenic cells within the osteohaematopoietic niche.
Identifiants
pubmed: 33182501
pii: cells9112443
doi: 10.3390/cells9112443
pmc: PMC7697865
pii:
doi:
Substances chimiques
Cytokines
0
FLT3 protein, human
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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