CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions.

Autor: McClain KL; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Picarsic J; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Chakraborty R; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Zinn D; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Lin H; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Abhyankar H; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Scull B; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Shih A; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Lim KPH; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.; Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas., Eckstein O; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Lubega J; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Peters TL; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.; Department of Pathology, Baylor College of Medicine, Houston, Texas., Olea W; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Burke T; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Ahmed N; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Hicks MJ; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.; Department of Pathology, Baylor College of Medicine, Houston, Texas., Tran B; Department of Radiology, Baylor College of Medicine, Houston, Texas., Jones J; Department of Radiology, Baylor College of Medicine, Houston, Texas., Dauser R; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas., Jeng M; Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California., Baiocchi R; Department of Internal Medicine, The Ohio State University, Columbus, Ohio., Schiff D; Department of Pediatrics, University of California-San Diego, La Jolla, California., Goldman S; Medical City Children's Hospital, Dallas Texas and Texas Oncology, Pennsylvania., Heym KM; Department of Pediatrics, Cook Children's Medical Center, Fort Worth, Texas., Wilson H; Department of Pathology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas., Carcamo B; Department of Pediatrics, Texas Tech University Health Sciences Center El Paso, El Paso, Texas., Kumar A; Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Rodriguez-Galindo C; St. Jude Children's Research Hospital, Memphis, Tennessee., Whipple NS; St. Jude Children's Research Hospital, Memphis, Tennessee., Campbell P; St. Jude Children's Research Hospital, Memphis, Tennessee., Murdoch G; Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Kofler J; Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Heales S; Chemical Pathology, Great Ormond Street Hospital for Children, London, UK., Malone M; Laboratory Medicine, Great Ormond Street Hospital for Children, London, UK., Woltjer R; Layton Aging and Alzheimer's Disease Center, Oregon Health and Science University, Portland, Oregon., Quinn JF; Layton Aging and Alzheimer's Disease Center, Oregon Health and Science University, Portland, Oregon., Orchard P; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota., Kruer MC; Barrow Neurological Institute, Phoenix Children's Hospital; Child Health, Neurology & Genetics, University of Arizona College of Medicine, Phoenix, Arizona., Jaffe R; Department of Pathology, Magee-Women's Hospital of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Manz MG; Division of Hematology, University of Zurich, University Hospital Zurich, Zurich, Switzerland., Lira SA; Immunology Institute, Icahn School of Medicine, New York, New York., Parsons DW; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas., Merad M; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine, New York, New York., Man TK; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Allen CE; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2018 Jun 15; Vol. 124 (12), pp. 2607-2620. Date of Electronic Publication: 2018 Apr 06.
DOI: 10.1002/cncr.31348
Abstrakt: Background: Central nervous system Langerhans cell histiocytosis (CNS-LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH-ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS-LCH.
Methods: Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAFV600E DNA were analyzed in CSF from patients with CNS-LCH lesions compared with patients with brain tumors and other neurodegenerative conditions. Additionally, the presence of BRAFV600E was tested in peripheral mononuclear blood cells (PBMCs) as well as brain biopsies from LCH-ND patients, and the response to BRAF-V600E inhibitor was evaluated in 4 patients with progressive disease.
Results: Osteopontin was the only consistently elevated CSF protein in patients with CNS-LCH compared with patients with other brain pathologies. BRAFV600E DNA was detected in CSF of only 2/20 (10%) cases, both with LCH-ND and active lesions outside the CNS. However, BRAFV600E + PBMCs were detected with significantly higher frequency at all stages of therapy in LCH patients who developed LCH-ND. Brain biopsies of patients with LCH-ND demonstrated diffuse perivascular infiltration by BRAFV600E + cells with monocyte phenotype (CD14 + CD33 + CD163 + P2RY12 - ) and associated osteopontin expression. Three of 4 patients with LCH-ND treated with BRAF-V600E inhibitor experienced significant clinical and radiologic improvement.
Conclusion: In LCH-ND patients, BRAFV600E + cells in PBMCs and infiltrating myeloid/monocytic cells in the brain is consistent with LCH-ND as an active demyelinating process arising from a mutated hematopoietic precursor from which LCH lesion CD207 + cells are also derived. Therapy directed against myeloid precursors with activated MAPK signaling may be effective for LCH-ND. Cancer 2018;124:2607-20. © 2018 American Cancer Society.
(© 2018 American Cancer Society.)
Databáze: MEDLINE
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