Differential survival of AML subpopulations in NOD/SCID mice
Objective - Leukemia-initiating cells can retrospectively be defined by tumorigenicity in immunodeficient mice and be characterized by surface markers. The latter still being discussed for acute myeloid leukemia (AML), nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice were used to ev...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[February 2011]
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| In: |
Experimental hematology
Year: 2011, Volume: 39, Issue: 2, Pages: 250-263 |
| ISSN: | 0531-5573 |
| DOI: | 10.1016/j.exphem.2010.10.010 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.exphem.2010.10.010 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0301472X10005485 
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| Author Notes: | Mario Schubert, Nicolás Herbert, Isabel Taubert, Dan Ran, Rahul Singh, Volker Eckstein, Mario Vitacolonna, Anthony D. Ho, Margot Zöller |
| Summary: | Objective - Leukemia-initiating cells can retrospectively be defined by tumorigenicity in immunodeficient mice and be characterized by surface markers. The latter still being discussed for acute myeloid leukemia (AML), nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice were used to evaluate long-time reconstitution and expansion of AML subpopulations. - Materials and Methods - Bone marrow cells from patients with AML were separated according to CD34 expression, aldehyde dehydrogenase (ALDH) activity, and divisional kinetics in comparison to cord blood−derived CD34+ hematopoietic stem cells, evaluating survival and expansion in NOD/SCID mice. The AML long-term surviving capacity of subpopulations recovered from NOD/SCID mice was confirmed by ex vivo survival. - Results - AML mononuclear cells were detected in bone marrow and spleen of NOD/SCID mice 12 weeks after transplantation. The majority of recovered cells were CD34+ and significantly more CD34+ cells were recovered after application of ALDHbright (high ALDH activity), CD34+, or slowly dividing (PKHbright) than after ALDHdim, CD34−, or fast dividing (PKHdim) cell application. CD123+, CD63+, and CD44v7+ cells were also more abundant after the transfer of ALDHbright or CD34+ AML mononuclear cells. In the spleen, large AML cell clusters were only recovered after ALDHbright, CD34+, or PKHbright cell transfer. Importantly, in secondary long-term in vitro cultures, quite exclusively CD34+ AML mononuclear cells survived and expanded. - Conclusions - Separation of ALDHbright, CD34+, or PKHbright cells enriches for AML long-term surviving capacity, which reside in the CD34+ subpopulation, as rather exclusively CD34+ cells survived and expanded in vivo and ex vivo. Long-term survival capacity may be supported by CD44v7 expression. |
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| Item Description: | Gesehen am 27.10.2022 |
| Physical Description: | Online Resource |
| ISSN: | 0531-5573 |
| DOI: | 10.1016/j.exphem.2010.10.010 |