2020
DOI: 10.3390/cells9112443
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Aberrant Bone Homeostasis in AML Is Associated with Activated Oncogenic FLT3-Dependent Cytokine Networks

Abstract: 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 qual… Show more

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Cited by 3 publications
(6 citation statements)
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“…81 Furthermore, FLT3-ITD-positive mice showed alterations in bone morphology suggesting a possible impact of aberrant oncogenic FLT3 signaling on the process controlling bone homeostasis. 85,86 Kumar and colleagues 66 noted that AML patients present an increase in exosome secretion, which correlates with the reduction of OCN plasma levels. Moreover, transplantation of AML-derived exosomes induces in the murine BM microenvironment alterations similar to those described for mice engrafted with AML cells (eg, block of osteolineage maturation and reduced bone formation).…”
Section: Evidence Of Aml-induced Stromal Niche Reprogramming From Ani...mentioning
confidence: 98%
See 2 more Smart Citations
“…81 Furthermore, FLT3-ITD-positive mice showed alterations in bone morphology suggesting a possible impact of aberrant oncogenic FLT3 signaling on the process controlling bone homeostasis. 85,86 Kumar and colleagues 66 noted that AML patients present an increase in exosome secretion, which correlates with the reduction of OCN plasma levels. Moreover, transplantation of AML-derived exosomes induces in the murine BM microenvironment alterations similar to those described for mice engrafted with AML cells (eg, block of osteolineage maturation and reduced bone formation).…”
Section: Evidence Of Aml-induced Stromal Niche Reprogramming From Ani...mentioning
confidence: 98%
“…Osteoblastic inhibition by leukemia seems to be mediated by chemokine CCL3, which is increased in malignant BM cells, both in leukemic mice and patients 81 . Furthermore, FLT3‐ITD‐positive mice showed alterations in bone morphology suggesting a possible impact of aberrant oncogenic FLT3 signaling on the process controlling bone homeostasis 85,86 …”
Section: Bm Microenvironment Alterations or Hsc Mutations: A Chicken ...mentioning
confidence: 99%
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“…The bone marrow (BM) microenvironment constitutes a complex multicellular network that includes endothelial, perivascular, mesenchymal, osteo‐lineage, and neuronal cells, all contributing to the homeostasis of the haematopoietic system and haematopoietic stem cells (HSC) 9–13 . In animal models, AML is associated with significant alterations within the BM microenvironment, 9,11–20 including gradual loss of endosteal and vascular niches 21–26 .…”
Section: Introductionmentioning
confidence: 99%
“…8 The bone marrow (BM) microenvironment constitutes a complex multicellular network that includes endothelial, perivascular, mesenchymal, osteo-lineage, and neuronal cells, all contributing to the homeostasis of the haematopoietic system and haematopoietic stem cells (HSC). [9][10][11][12][13] In animal models, AML is associated with significant alterations within the BM microenvironment, 9,[11][12][13][14][15][16][17][18][19][20] including gradual loss of endosteal and vascular niches. [21][22][23][24][25][26] Homing and engraftment of AML stem cells to osteoblast-rich BM areas protects against chemotherapy-induced apoptosis, 24 and leukaemic cell growth disrupts the normal BM stroma and creates an abnormal niche that can sequester malignant HSCs.…”
Section: Introductionmentioning
confidence: 99%