Mayo Clinic Laboratory and Pathology Research Roundup: March 20

By Kelley Luedke • March 20, 2017

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The Research Roundup provides an overview of the past week’s research from Mayo Medical Laboratories consultants, including featured abstracts and complete list of published studies and reviews.

Featured Abstract

AKT-Phosphorylated FOXO1 Suppresses ERK Activation and Chemoresistance by Disrupting IQGAP1-MAPK Interaction

Nuclear FOXO proteins act as tumor suppressors by transcriptionally activating genes involved in apoptosis and cell cycle arrest, and these anticancer functions are inhibited by AKT-induced phosphorylation and cytoplasmic sequestration of FOXOs. Mayo Clinic researchers found that, after AKT-mediated phosphorylation at serine 319, FOXO1 binds to IQGAP1, a hub for activation of the MAPK pathway, and impedes IQGAP1-dependent phosphorylation of ERK1/2 (pERK1/2). Conversely, decreased FOXO1 expression increases pERK1/2 in cancer cell lines and correlates with increased pERK1/2 levels in patient specimens and disease progression. Treatment of cancer cells with PI3K inhibitors or taxane causes FOXO1 localization in the nucleus, increased expression of pERK1/2, and drug resistance. These effects are reversed by administering a small FOXO1-derived phospho-mimicking peptide inhibitor in vitro and in mice. These results show a tumor suppressor role of AKT-phosphorylated FOXO1 in the cytoplasm and suggest that this function of FOXO1 can be harnessed to overcome chemoresistance in cancer. The study was published in EMBO Journal.

Published to PubMed This Week

• Pooled Clustering of High-Grade Serous Ovarian Cancer Gene Expression Leads to Novel Consensus Subtypes Associated With Survival and Surgical Outcomes
  Clinical Cancer Research
• BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
  Cancer Research
  
• Using Biomarkers to Guide Heart Failure Therapy
  Clinical Chemistry
• Intracranial Myxoid Mesenchymal Tumors with EWSR1- CREB Family Gene Fusions: Myxoid Variant of Angiomatoid Fibrous Histiocytoma or Novel Entity
  Brain Pathology
• Assessment of Renal Response With Urinary Exosomes in Patients With AL Amyloidosis: A Proof of Concept
  American Journal of Hematology
• GDNF Schwann Cells in Hydrogel Scaffolds Promote Regional Axon Regeneration, Remyelination and Functional Improvement After Spinal Cord Transection in Rats
  Journal of Tissue Engineering and Regenerative Medicine
• WHO 2016 Classification: Changes and Advancements in the Diagnosis of Miscellaneous Primary CNS Tumours
  Neuropathology and Applied Neurobiology
• Prognostic Impact of Bone Marrow Fibrosis in Polycythemia Vera: Validation of the IWG-MRT Study and Additional Observations
  Blood Cancer Journal
• Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial
  Stem Cells Translational Medicine
• Genomic Tests to Guide Prostate Cancer Management Following Diagnosis
  Expert Review of Molecular Diagnostics
• Accuracy of 18-F FDG PET/CT to Detect Bone Marrow Clearance in Patients with Peripheral T-cell Lymphoma - Tissue Remains the Issue
  Leukemia & Lymphoma
• Cellular and Molecular Defects in a Patient with Hermansky-Pudlak Syndrome Type 5
  PLoS One
• Incidental EBV-Positivity in Paediatric Post-Transplant Specimens Demonstrates the Need for Stringent Criteria for Diagnosing Post-Transplant Lymphoproliferative Disorders
  Journal of Clinical Pathology
• IgG4-Related Tubulointerstitial Nephritis
  Advances in Chronic Kidney Disease
• Diagnosis of Acute Cellular Rejection and Antibody-Mediated Rejection on Lung Transplant Biopsies: A Perspective From Members of the Pulmonary Pathology Society
  Archives of Pathology & Laboratory Medicine
• Detection and Differentiation of Norovirus Genogroups I and II From Clinical Stool Specimens Using Real-Time PCR
  Diagnostic Microbiology and Infectious Disease
• Therapeutic Plasma Exchange for Perioperative Management of Patients With Congenital Factor XI Deficiency
  Journal of Clinical Apheresis
• Analytical Performance of Three Whole Blood Point-of-Care Lactate Devices Compared to Plasma Lactate Comparison Methods and a Flow-Injection Mass Spectrometry Method
  Clinical Biochemistry
• Long-Standing Crohn's Disease and its Implication on Anal Squamous Cell Cancer Management
  International Journal of Colorectal Disease
• Family History of Colorectal Cancer and its Impact on Survival in Patients With Resected Stage III Colon Cancer: Results From NCCTG Trial N0147 (Alliance)
  Journal of Gastrointestinal Oncology
• A Case of Acute Myeloid Leukemia With e6a2 BCR-ABL Fusion Transcript Acquired After Progressing from Chronic Myelomonocytic Leukemia
  Leukemia Research Reports
• Clinical and Surgical Management of a Congenital Type II Split Cord Malformation Presenting with Progressive Cranial Neuropathies: Case Report
  Journal of Neurosurgery: Pediatrics

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.