Original Article
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World J Stem Cells. Oct 26, 2013; 5(4): 196-204
Published online Oct 26, 2013. doi: 10.4252/wjsc.v5.i4.196
Mobilization of CD34+CD38- hematopoietic stem cells after priming in acute myeloid leukemia
Adriana Plesa, Youcef Chelghoum, Eve Mattei, Hélène Labussière, Mohamed Elhamri, Giovanna Cannas, Stéphane Morisset, Inès Tagoug, Mauricette Michallet, Charles Dumontet, Xavier Thomas
Adriana Plesa, Eve Mattei, Charles Dumontet, Laboratoire de Cytologie et d’Immunologie, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre Bénite, France
Youcef Chelghoum, Hélène Labussière, Giovanna Cannas, Mauricette Michallet, Xavier Thomas, Department of Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre Bénite, France
Mohamed Elhamri, Stéphane Morisset, Unité de Recherche Clinique, Service d’Hématologie, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, 69495 Pierre Bénite, France
Inès Tagoug, INSERM U590, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, Université Lyon-I, 69495 Lyon, France
Author contributions: Plesa A was responsible for co-ordinating immunophenotyping data and participated in the analysis and interpretation of data; Mattei E and Tagoug I participated in the collection of immunophenotyping data; Morisset S performed statistical analyses; Chelghoum Y, Labussière H and Cannas G included patients and collected samples; Elhamri M collected the data and provided technical support; Michallet M and Dumontet C reviewed the manuscript and gave final approval; Thomas X included patients, collected samples, interpreted the data and wrote the manuscript.
Correspondence to: Xavier Thomas, MD, PhD, Department of Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pavillon Marcel Bérard, Bât.1G, 165 chemin du Grand Revoyet, 69495 Pierre Bénite, France. xavier.thomas@chu-lyon.fr
Telephone: +33-478862235 Fax: +33-472678880
Received: May 2, 2013
Revised: June 23, 2013
Accepted: July 30, 2013
Published online: October 26, 2013
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+CD38low 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, Leukemia stem cell, Immunophenotype, Priming, Timed sequential chemotherapy

Core tip: Timed sequential chemotherapy and priming with hematopoietic growth factors have been recently used in the treatment of acute myeloid leukemia in order to mobilize more leukemic cells in the cell cycle and therefore improve the cytotoxic effect of chemotherapy. In this paper, we looked the impact of this type of treatment in a small series of patients on the mobilization of different subsets of CD34+ cells involving “bulk” leukemic cells and more ‘‘immature’’ leukemic cells.