title: Direct confirmation of quiescence of CD34+CD38- leukemia stem cell populations using single cell culture, their molecular signature and clinicopathological implications.
abstract: BACKGROUND
  The proliferating activity of a single leukemia stem cell and the molecular mechanisms for their quiescent property remain unknown, and also their prognostic value remains a matter of debate. Therefore, this study aimed to demonstrate the quiescence property and molecular signature of leukemia stem cell and their clinicopathological implications.
  
  
  METHODS
  Single cell sorting and culture were performed in the various sets of hematopoietic stem cells including CD34+CD38- acute myeloid leukemia (AML) cell population (ASCs) from a total of 60 patients with AML, and 11 healthy controls. Their quiescence related-molecular signatures and clinicopathological parameters were evaluated in AML patients.
  
  
  RESULTS
  Single cell plating efficiency of ASCs was significantly lower (8.6%) than those of normal hematopoietic stem cells i.e.: cord blood, 79.0%; peripheral blood, 45.3%; and bone marrow stem cell, 31.1%. Members of the TGFβ super-family signaling pathway were most significantly decreased; as well as members of the Wnt, Notch, pluripotency maintenance and hedgehog pathways, compared with non ASC populations. mtDNA copy number of ASCs was significantly lower than that of corresponding other cell populations. However, our data couldn't support the prognostic value of the ASCs in AML.
  
  
  CONCLUSIONS
  ASCs showed remarkable lower plating efficiency and slower dividing properties at the single cell level. This quiescence is represented as a marked decrease in the mtDNA copy number and also linked with down-regulation of genes in various molecular pathways.
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, South Korea. dana_clinic@naver.com.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Won
authors.affiliation: College of Korean Medicine, Dongshin University, Naju, South Korea. KimHR@chonnam.ac.kr.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, South Korea. parkry@hanmail.net.
authors.forename: Ra-Young
authors.initials: RY
authors.lastname: Park
authors.affiliation: Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, South Korea. zebrafish@chonnam.ac.kr.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, South Korea. shinjh@chonnam.ac.kr.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, South Korea. spsuh@chonnam.ac.kr.
authors.forename: Soon-Pal
authors.initials: SP
authors.lastname: Suh
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, South Korea. dwryang@chonnam.ac.kr.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Ryang
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany. michael.szardenings@izi.fraunhofer.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Szardenings
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, South Korea. mgshin@chonnam.ac.kr.|Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, South Korea. mgshin@chonnam.ac.kr.|Environment Health Center for Childhood Leukemia and Cancer, Chonnam National University Hwasun Hospital, Hwasun, South Korea. mgshin@chonnam.ac.kr.
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D004272:DNA, Mitochondrial; D005260:Female; D005434:Flow Cytometry; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D016192:Resting Phase, Cell Cycle / Q000235:genetics*; D014410:Tumor Stem Cell Assay; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D004272:DNA, Mitochondrial; D051997:ADP-ribosyl Cyclase 1