Differential survival of AML subpopulations in NOD/SCID mice

• Verfasst von: Schubert, Mario [VerfasserIn]
• Verfasst von: Herbert, Nicolás Nathaniel [VerfasserIn]
• Verfasst von: Hoffmann, Isabel [VerfasserIn]
• Verfasst von: Ran, Dan [VerfasserIn]
• Verfasst von: Singh, Rahul [VerfasserIn]
• Verfasst von: Eckstein, Volker [VerfasserIn]
• Verfasst von: Vitacolonna, Mario [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Zöller, Margot [VerfasserIn]
• Titel: Differential survival of AML subpopulations in NOD/SCID mice
• Verf.angabe: Mario Schubert, Nicolás Herbert, Isabel Taubert, Dan Ran, Rahul Singh, Volker Eckstein, Mario Vitacolonna, Anthony D. Ho, Margot Zöller
• E-Jahr: 2011
• Jahr: [February 2011]
• Umfang: 18 S.
• Illustrationen: Illustrationen, Diagramme
• Fussnoten: Gesehen am 27.10.2022
• Titel Quelle: Enthalten in: Experimental hematology
• Ort Quelle: Kidlington [u.a] : Elsevier, 1964
• Jahr Quelle: 2011
• Band/Heft Quelle: volume 39, issue 2 (February 2011), Seite 250-263, e1-e4
• ISSN Quelle: 0531-5573
• ISSN Quelle: 0301-472X
• DOI: doi:10.1016/j.exphem.2010.10.010
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1820166260

Abstract

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.