Mobilization of CD34(+)CD38(-) hematopoietic stem cells after priming in acute myeloid leukemia

World J Stem Cells. 2013 Oct 26;5(4):196-204. doi: 10.4252/wjsc.v5.i4.196.

Abstract

Aim: To evaluate quantitatively and qualitatively the different CD34(+) cell subsets after priming by chemotherapy granulocyte colony-stimulating factor (± G-CSF) in patients with acute myeloid leukemia.

Methods: Peripheral blood and bone marrow samples were harvested in 8 acute myeloid leukemia patients during and after induction chemotherapy. The CD34/CD38 cell profile was analyzed by multi-parameter flow cytometry. Adhesion profile was made using CXC chemokine receptor 4 (CXCR4) (CD184), VLA-4 (CD49d/CD29) and CD47.

Results: Chemotherapy ± G-CSF mobilized immature cells (CD34(+)CD38(-) population), while the more mature cells (CD34(+)CD38(low) and CD34(+)CD38(+) populations) decreased progressively after treatment. Circulating CD34(+) cells tended to be more sensitive to chemotherapy after priming with G-CSF. CD34(+) cell mobilization was correlated with a gradual increase in CXCR4 and CD47 expression, suggesting a role in cell protection and the capacity of homing back to the marrow.

Conclusion: Chemotherapy ± G-CSF mobilizes into the circulation CD34(+) bone marrow cells, of which, the immature CD34(+)CD38(-) cell population. Further manipulations of these interactions may be a means with which to control the trafficking of leukemia stem cells to improve patients' outcomes.

Keywords: Acute myeloid leukemia; Immunophenotype; Leukemia stem cell; Priming; Timed sequential chemotherapy.