Detection of AML-specific TP53 mutations in bone marrow–derived mesenchymal stromal cells cultured under hypoxia conditions
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TP53 mutations are early events in the pathogenesis of acute myeloid leukemia (AML) and TP53-mutated AML has recently been classified as a distinct subentity [1, 2, 3]. An increasing number of reports postulate that the bone marrow (BM) microenvironment of patients with myeloid malignancies contributes to both leukemogenesis and therapeutic resistance . As disease-specific, somatic aberrations have been reported in cells of the BM microenvironment in these disorders [5, 6], we hypothesized that BM-derived mesenchymal stromal cells (BM-MSCs) are also affected by leukemia-specific mutations in patients with TP53-mutated AML.
The detection of somatic, leukemia–specific TP53 mutations in BM-MSCs of AML patients may indicate that these mutations have arisen in common mesodermal ancestors of hematopoietic stem and progenitor cells and BM-MSCs . It further supports the concept of TP53 mutations being early events of acute myeloid leukemogenesis. The demonstration of BM-MSCs affected by leukemia-specific mutations—albeit at low VAFs—might also have practical implications as these cell types are increasingly used as a source of germline, control DNA . Future work will focus on the functional role of the bone marrow microenvironment in this distinct AML subentity.
This work was supported by “Anna-Maurer Fund” and the Austria Science Fund FWF (P 31430-B26).
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Conflict of interest
The authors declare that they have no conflict of interest.
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