2019 Recipient
Area: Pediatrics – Hematology/Oncology
Associate Professor of Pediatrics, Division of Hematology/Oncology; Co-Director of TXCH Histiocytosis and Lymphoma Programs; Director of Research, Global HOPE; Member, Dan L Duncan Comprehensive Cancer Center
Dr. Allen’s work has focused on defining mechanisms of pathogenesis of Langerhans cell histiocytosis (LCH). LCH is characterized by granulomatous lesions with typical CD207+ dendritic cells that may arise as isolated lesions or disseminated life-threatening disease. Uncertain classification of LCH as a disorder of immune dysregulation versus neoplastic disease has blocked access to research support from National Cancer Institute-supported organizations, limiting opportunities to improve outcomes for patients through clinical trials. Dr. Allen’s research at Baylor College of Medicine has redefined LCH as a bona fide myeloid neoplastic disorder arising from hematopoietic precursors with activating MAPK pathway mutations. In a recent study published in Cancer, his team investigated the causes of LCH-associated neurodegeneration. They identified BRAF-V600E+ cells in peripheral blood and in brain biopsies of patients with LCH-ND, and patients treated with vemurafenib experienced dramatic clinical and radiologic improvement. This study determined that LCH-ND is a process caused by the same hematopoietic clones that drive systemic LCH lesion formation. While previous work used lineage tracing with MAPK pathway mutations to identify differentiation pathways of LCH, the functional consequences of MAPK activation in myeloid precursors were not known. In a study published in the Journal of Experimental Medicine, they determined that MAPK hyper-activation in myeloid dendritic cells abrogates CCR7 expression and up-regulates proteins that inhibit apoptosis, trapping activated pathologic DC resistant to cell death in lesions. The paradigm-changing work by Dr. Allen and colleagues has re-defined LCH as a myeloproliferative disorder. This work has not only uncovered novel therapeutic opportunities, but also it has contributed to the NCI including
Dr. Allen’s nomination was based on the following publications:
McClain KL, Picarsic J, Chakraborty R, Zinn D, Lin H, Abhyankar H, Scull B, Shih A, Lim KPH, Eckstein O, Lubega J, Peters TL, Olea W, Burke T, Ahmed N, Hicks MJ, Tran B, Jones J, Dauser R, Jeng M, Baiocchi R, Schiff D, Goldman S, Heym KM, Wilson H, Carcamo B, Kumar A, Rodriguez-Galindo C, Whipple NS, Campbell P, Murdoch G, Kofler J, Heales S, Malone M, Woltjer R, Quinn JF, Orchard P, Kruer MC, Jaffe R, Manz MG, Lira SA, Parsons DW, Merad M, Man TK, Allen CE. CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions. Cancer. 2018 Jun 15;124(12):2607-2620. doi: 10.1002/cncr.31348. Epub 2018 Apr 6. PubMed PMID: 29624648; PubMed Central PMCID: PMC6289302.
Hogstad B, Berres ML, Chakraborty R, Tang J, Bigenwald C, Serasinghe M, Lim KPH, Lin H, Man TK, Remark R, Baxter S, Kana V, Jordan S, Karoulia Z, Kwan WH, Leboeuf M, Brandt E, Salmon H, McClain K, Poulikakos P, Chipuk J, Mulder WJM, Allen CE, Merad M. RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med. 2018 Jan 2;215(1):319-336. doi: 10.1084/jem.20161881.
Allen C, Merad M, McClain K. Langerhans-Cell Histiocytosis. August 30, 2018. N Engl J Med 2018; 379:856-868. DOI: 10.1056/NEJMra1607548.
