Direct confirmation of quiescence of CD34+CD38-leukemia stem cellpopulations using single cell culture, their molecular signature andclinicopathological implications
| Autor: | Seok-Yong Choi, Eun Jeong Won, Ra-Young Park, Michael Szardenings, Soon Pal Suh, Jong Hee Shin, Myung-Geun Shin, Dong-Wook Ryang, Hye-Ran Kim |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Cancer Research Adolescent Cell Culture Techniques Gene Dosage CD34 Antigens CD34 DNA Mitochondrial Resting Phase Cell Cycle Young Adult Genetics Humans Medicine prognostic value quiescence Tumor Stem Cell Assay Aged Aged 80 and over Leukemia Gene Expression Regulation Leukemic business.industry Gene Expression Profiling Myeloid leukemia Bone Marrow Stem Cell CD34+CD38- AML cell Middle Aged Flow Cytometry Prognosis medicine.disease molecular signature ADP-ribosyl Cyclase 1 CD34+CD38-AML cell Quiescence Molecular signature Prognostic value Leukemia Myeloid Acute Haematopoiesis Oncology Case-Control Studies Cord blood Neoplastic Stem Cells Cancer research Female Stem cell business Research Article |
| Zdroj: | BMC CANCER(15) BMC Cancer |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1233-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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