Despite high remission rates after therapy, 60% to 70% of patients with acute myeloid leukemia (AML) do not survive 5 years after their initial diagnosis. The main cause of treatment failures may be insufficient eradication of a subpopulation of leukemic stem-like cells (LSC), which are thought to be responsible for relapse by giving rise to more differentiated leukemic progenitors (LP). To address the need for therapeutic targets in LSCs, we compared microRNA (miRNA) expression patterns in highly enriched healthy CD34
<p>XLSX file - 11KB, MicroRNA-126 is highly expressed in core binding factor AML: qRT-PCR results of miR-126 in CD34+CD38-ALDHlow/dim LSC and CD34+CD38+ALDHlow/dim leukemic progenitors in 18 AML patients. Cytogenetics indicates the presence of a CBF karyotype. Values are calculated using the dCT method with the mean of the LSC ct-values set to 1. Average and ratio, respectively indicates the averages and ratios of miR-126 expression in the LSC and progenitor fractions. CBF leukemias show higher expression of miR-126 compared to non-CBF leukemias. However the ratio of miR-126 expression between LSC and leukemic progenitors is not different in CBF and non-CBF leukemias.</p>
<p>XLSX file - 15KB, MicroRNAs differentially expressed between LSC and HSC (at least 2 out of 3 patients): Upper: MicroRNA expression ratios between CD34+CD38-ALDHlow/dim(LSC) and CD34+CD38-ALDHhigh (HSC) populations obtained from microarray analysis. The average ratio is calculated over all 3 analyzable patients. Number of patients indicate the number of patients that show significant differential expression for that microRNA. Lower: Average and standard deviations of all ratios between LSC and HSC per patient. 'Average + Stdev' and 'Average - Stdev', average plus or minus one time the standard deviation for each individual patient indicate the values used as cutoff for significant microRNAs per patients. Italic printed ratios represent non-significant microRNAs for that individual patient.</p>
<p>PDF file - 93KB, Validation of microarray by qRT-PCR: Surplus RNA from LSC and progenitor populations that remained after array hybridization was used for the validation of the microarray results. MicroRNA expression analysis was performed by qRT-PCR using microRNA specific primers and RNU48 as internal control. Fold change was calculated using ddCT-method. qRT-PCR validated the results obtained from microarray analysis. CD34+CD38- LSC show higher expression of miR-22, miR-126, miR-150, miR-335 and lower expression of miR-886-3p compared to CD34+CD38+ leukemic progenitors. Blue bars, LSC; Red bars, leukemic progenitors.</p>
<p>XLSX file - 9KB, Patient characteristics and stem cell frequencies: Patient characteristics and stem cell frequencies of samples used for miRNA expression profiling using microarray. Molecular aberrancy indicates the aberrancy as detected by routine molecular analysis of the patient at diagnosis. '-' indicates no abnormalities found in all molecular analysis tested (e.g. t(8;21), t(15;17), inv(16), NPM1, EVI1, CEBPA, and MLL). The fraction HSC within the CD34+ population indicates the CD34+CD38-ALDHhighLAPneg cells within the CD45+CD34+ cell compartment. For LSC the fraction of CD34+CD38-ALDHlow/dim cells were used. F, female; M, male; WBC, white blood cell count.</p>
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