title: Microarray analyses of oral punch biopsies from acute myeloid leukemia (AML) patients treated with chemotherapy.
abstract: OBJECTIVE
  Understanding the pathogenesis of chemotherapy-induced oral mucositis (CIOM) is vital to develop therapies for this common, dose-limiting side effect of cancer treatment. We investigated molecular events in CIOM from buccal mucosa tissue collected before and 2 days after chemotherapy from patients with acute myeloid leukemia (AML) and healthy controls by microarray analysis.
  
  
  METHODS
  Microarray analysis was performed using Human Genome U133 Plus 2.0 Array on buccal mucosa punch biopsies from patients with AML before (n = 4) or after chemotherapy (n = 4), and from healthy controls (n = 3). Following Robust Multichip Average (RMA) normalization, we applied Linear Models for Microarray data (LIMMA) and Significance Analysis of Microarrays (SAM) for data analysis using the TM4/TMeV v4.5.1 program.
  
  
  RESULTS
  LIMMA and SAM identified genes potentially affected by the presence of AML, including homeodomain-interacting protein kinase 1 (HIPK1), mex-3 homolog D (MEX3D), and genes potentially affected by chemotherapy, including argininosuccinate synthase 1 (ASS1), notch homolog 1 (NOTCH1), zinc transporter ZIP6 (SLC39A6), and TP53-regulated inhibitor of apoptosis 1 (TRIAP1). The expression of 2 genes with potential biological significance in oral mucositis, ASS1 and SLC39A6 (alias LIV-1), was confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR).
  
  
  CONCLUSIONS
  Our results suggest that AML-specific deregulated immune responses and inflammatory tissue damage to the oral mucosa caused by chemotherapy may not be overcome by the natural cellular repair processes and therefore contribute to CIOM.
authors.affiliation: Cannon Research Center, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Jean-Luc C
authors.initials: JL
authors.lastname: Mougeot
authors.forename: Farah K
authors.initials: FK
authors.lastname: Bahrani-Mougeot
authors.forename: Peter B
authors.initials: PB
authors.lastname: Lockhart
authors.forename: Michael T
authors.initials: MT
authors.lastname: Brennan
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001124:Argininosuccinate Synthase / Q000032:analysis / Q000187:drug effects; D001324:Autoantigens / Q000032:analysis / Q000187:drug effects; D001707:Biopsy, Needle; D002352:Carrier Proteins / Q000032:analysis / Q000187:drug effects; D027682:Cation Transport Proteins / Q000032:analysis / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000187:drug effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000187:drug effects; D046228:Microarray Analysis / Q000379:methods*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000032:analysis / Q000187:drug effects; D051881:Receptor, Notch1 / Q000032:analysis / Q000187:drug effects; D054840:Retinol-Binding Proteins, Cellular / Q000032:analysis / Q000187:drug effects; D012261:Ribonucleoproteins / Q000032:analysis / Q000187:drug effects; D013280:Stomatitis / Q000139:chemically induced* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000187:drug effects; D016335:Zinc Fingers / Q000187:drug effects / Q000235:genetics; D000097585:SS-B Antigen
chemical_list: D000970:Antineoplastic Agents; D001124:Argininosuccinate Synthase; D001324:Autoantigens; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1; D054840:Retinol-Binding Proteins, Cellular; D012261:Ribonucleoproteins; D016159:Tumor Suppressor Protein p53; D000097585:SS-B Antigen; C075176:AHNAK protein, human; C497761:NOTCH1 protein, human; C518456:RBP1 protein, human; C418627:SLC39A6 protein, human; C498536:TRIAP1 protein, human; C115114:HIPK2 protein, human; C543644:HIPK1 protein, human