<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Seipel K</dc:creator>
  <dc:creator>Messerli C</dc:creator>
  <dc:creator>Wiedemann G</dc:creator>
  <dc:creator>Bacher U</dc:creator>
  <dc:creator>Pabst T</dc:creator>
  <dc:date>2020</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">BACKGROUND
The meningioma-1 (MN1) gene is expressed in hematopoietic CD34+ cells and down-regulated during myeloid differentiation. MN1 overexpression has been linked to shorter overall and disease free survival in AML patients treated with intensive induction chemotherapy. MN1 overexpression may still be an adverse prognostic marker in AML patients treated with autologous stem cell transplant (auto-SCT) after intensive induction chemotherapy.


METHODS
We retrospectively analysed 54 peripheral blood mononuclear cell (PBMC) samples of AML patients who received auto-SCT at remission (CR1) after intensive induction chemotherapy. MN1 and putative MN1-associated mRNAs, as well as MN1-associated micro-RNAs were assessed at diagnosis in peripheral blood mononuclear cells using Taqman gene expression assays.


RESULTS
AML patients with elevated MN1 or FoxP1 gene expression at diagnosis had a significantly shorter progression-free and overall survival after intensive induction chemo-therapy and auto-SCT. The presence of the favourable risk NPM1 mutation associated with reduced MN1 gene expression. In contrast to MN1 and FOXP1, elevated expression of the putative tumor suppressive micro-RNA hsa-miR-181a-5p was predictive for positive outcome. Correlation analysis of MN1 with myeloid gene expression levels revealed association of MN1 and BMI-1, CD34, FOXP1 and MDM2 expression. Analysis of non-coding RNAs revealed an inverse correlation of MN1 with hsa-miR-20a-5p and hsa-miR-181b-5p expression.


CONCLUSIONS
MN1, FOXP1 and hsa-miR-181a-5p are prognostic markers in AML patients treated with intensive induction chemotherapy and auto-SCT. While MDM2 is a validated therapeutic target, the transcription factors MN1 and FOXP1, and the chromatin modulator BMI-1 are potential therapeutic targets in the treatment of AML. The tumor suppressor hsa-miR-181a-5p may be a candidate miRNA mimic for therapeutic use.</dc:description>
  <dc:identifier>https://sonar.ch/global/documents/46824</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.leukres.2020.106296</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/31927137</dc:relation>
  <dc:source>Leukemia research. - 2020</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">Acute myeloid leukemia (AML)</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Autologous stem cell transplantation (auto-SCT)</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Leukemic stem cell (LSC)</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Stem cell surface marker CD34</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Transcription co-regulator Meningioma-1 (MN1)</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Adult</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Aged</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Antineoplastic Combined Chemotherapy Protocols</dc:subject>
  <dc:subject xmlns:ns9="xml" ns9:lang="en">Biomarkers, Tumor</dc:subject>
  <dc:subject xmlns:ns10="xml" ns10:lang="en">Female</dc:subject>
  <dc:subject xmlns:ns11="xml" ns11:lang="en">Forkhead Transcription Factors</dc:subject>
  <dc:subject xmlns:ns12="xml" ns12:lang="en">Gene Expression Regulation, Neoplastic</dc:subject>
  <dc:subject xmlns:ns13="xml" ns13:lang="en">Hematopoietic Stem Cell Transplantation</dc:subject>
  <dc:subject xmlns:ns14="xml" ns14:lang="en">Humans</dc:subject>
  <dc:subject xmlns:ns15="xml" ns15:lang="en">Induction Chemotherapy</dc:subject>
  <dc:subject xmlns:ns16="xml" ns16:lang="en">Leukemia, Myeloid, Acute</dc:subject>
  <dc:subject xmlns:ns17="xml" ns17:lang="en">Male</dc:subject>
  <dc:subject xmlns:ns18="xml" ns18:lang="en">MicroRNAs</dc:subject>
  <dc:subject xmlns:ns19="xml" ns19:lang="en">Middle Aged</dc:subject>
  <dc:subject xmlns:ns20="xml" ns20:lang="en">Models, Biological</dc:subject>
  <dc:subject xmlns:ns21="xml" ns21:lang="en">Mutation</dc:subject>
  <dc:subject xmlns:ns22="xml" ns22:lang="en">Prognosis</dc:subject>
  <dc:subject xmlns:ns23="xml" ns23:lang="en">Repressor Proteins</dc:subject>
  <dc:subject xmlns:ns24="xml" ns24:lang="en">Retrospective Studies</dc:subject>
  <dc:subject xmlns:ns25="xml" ns25:lang="en">Trans-Activators</dc:subject>
  <dc:subject xmlns:ns26="xml" ns26:lang="en">Transplantation, Autologous</dc:subject>
  <dc:subject xmlns:ns27="xml" ns27:lang="en">Treatment Outcome</dc:subject>
  <dc:subject xmlns:ns28="xml" ns28:lang="en">Tumor Suppressor Proteins</dc:subject>
  <dc:subject xmlns:ns29="xml" ns29:lang="en">Young Adult</dc:subject>
  <dc:title xmlns:ns30="xml" ns30:lang="en">MN1, FOXP1 and hsa-miR-181a-5p as prognostic markers in acute myeloid leukemia patients treated with intensive induction chemotherapy and autologous stem cell transplantation.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>