Abstract:
:In contrast to well-established hierarchical concepts of tumor stem cells, leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia have not yet been phenotypically identified. Different subpopulations, as defined by surface markers, have shown equal abilities to reconstitute leukemia upon transplantation into immunodeficient mice. Using a non-obese diabetes/severe combined immunodeficiency human acute lymphoblastic leukemia mouse model and cell cycle analysis annotating cells to distinct cycle phases, we functionally characterized leukemia-initiating cells and found that cells in all stages of the cell cycle are able to reconstitute leukemia in vivo, with early cycling cells (G1blow population) exhibiting the highest leukemia-initiating potential. Interestingly, cells of the G2/M compartment, i.e. dividing cells, were less effective in leukemia reconstitution. Moreover, G1blow cells were more resistant to spontaneous or drug-induced cell death in vitro, were enriched for stem cell signatures and were less metabolically active, as determined by lower levels of reactive oxygen species, compared to G2/M stage cells. Our data provide new information on the biological properties of leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia and underline the concept of a stochastic model of leukemogenesis.
journal_name
Haematologicajournal_title
Haematologicaauthors
Trentin L,Queudeville M,Eckhoff SM,Hasan N,Münch V,Boldrin E,Seyfried F,Enzenmüller S,Debatin KM,Meyer LHdoi
10.3324/haematol.2017.167502subject
Has Abstractpub_date
2018-06-01 00:00:00pages
1008-1017issue
6eissn
0390-6078issn
1592-8721pii
haematol.2017.167502journal_volume
103pub_type
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