Differential survival of AML subpopulations in NOD/SCID mice

Exp Hematol. 2011 Feb;39(2):250-263.e4. doi: 10.1016/j.exphem.2010.10.010. Epub 2010 Nov 16.


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 ALDH(bright) (high ALDH activity), CD34(+), or slowly dividing (PKH(bright)) than after ALDH(dim), CD34(-), or fast dividing (PKH(dim)) cell application. CD123(+), CD63(+), and CD44v7(+) cells were also more abundant after the transfer of ALDH(bright) or CD34(+) AML mononuclear cells. In the spleen, large AML cell clusters were only recovered after ALDH(bright), CD34(+), or PKH(bright) cell transfer. Importantly, in secondary long-term in vitro cultures, quite exclusively CD34(+) AML mononuclear cells survived and expanded.

Conclusions: Separation of ALDH(bright), CD34(+), or PKH(bright) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Bone Marrow Cells / cytology
  • Cell Cycle
  • Cell Proliferation
  • Cell Separation
  • Cell Survival
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Leukemia, Myeloid, Acute*
  • Leukocytes, Mononuclear / cytology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Tumor Cells, Cultured


  • Antigens, CD34