Integrative Molecular Pathological Epidemiology of Congenital and Infant Acute Leukemia Heather Elizabeth Williams Nova Southeastern University

Integrative Molecular Pathological Epidemiology of Congenital and Infant Acute Leukemia Heather Elizabeth Williams Nova Southeastern University

Nova Southeastern University NSUWorks Health Sciences Program Student Theses, Department of Health Sciences Dissertations and Capstones 1-1-2019 Integrative Molecular Pathological Epidemiology of Congenital and Infant Acute Leukemia Heather Elizabeth Williams Nova Southeastern University This document is a product of extensive research conducted at the Nova Southeastern University College of Health Care Sciences. For more information on research and degree programs at the NSU College of Health Care Sciences, please click here. Follow this and additional works at: https://nsuworks.nova.edu/hpd_hs_stuetd Part of the Medicine and Health Sciences Commons All rights reserved. This publication is intended for use solely by faculty, students, and staff of oN va Southeastern University. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher. NSUWorks Citation Heather Elizabeth Williams. 2019. Integrative Molecular Pathological Epidemiology of Congenital and Infant Acute Leukemia. Doctoral dissertation. Nova Southeastern University. Retrieved from NSUWorks, College of Health Care Sciences – Health Science Department. (13) https://nsuworks.nova.edu/hpd_hs_stuetd/13. This Dissertation is brought to you by the Department of Health Sciences at NSUWorks. It has been accepted for inclusion in Health Sciences Program Student Theses, Dissertations and Capstones by an authorized administrator of NSUWorks. For more information, please contact [email protected]. The Integrative Molecular Pathological Epidemiology of Congenital and Infant Acute Leukemia Heather E. Williams, PhD(c), MS, PgD, ErCLG, CG(ASCP) CM MB CM Nova Southeastern University A Dissertation Study Submitted to Dr. Pallavi Patel College of Health Care Sciences In Partial Fulfillment for the Requirement for the Degree of Doctor of Philosophy in Health Sciences January 2019 Nova Southeastern University Dr. Pallavi Patel College of Health Care Sciences We hereby certify that this dissertation, submitted by Heather Williams conforms to acceptable standards and is fully adequate in scope and quality to fulfill the dissertation requirement for the degree of Doctor of Philosophy in Health Science. __________________________________________ ___________________ Akiva Turner PhD, JD, MPH Date Chairperson of Dissertation Committee __________________________________________ ___________________ Carol Lynn Chevalier DHSc, MPH Date Dissertation Committee Member __________________________________________ ___________________ Debra A. Dixon RDH, MS, DHSc Date Dissertation Committee Member Approved: __________________________________________ ___________________ Akiva Turner PhD, JD, MPH Date Program Director __________________________________________ ___________________ Akiva Turner PhD, JD, MPH Date Chair, Department of Health Science __________________________________________ ___________________ Stanley H. Wilson, P.T., Ed.D., CEAS Date Dean, Dr. Pallavi Patel College of Health Care Sciences Abstract Congenital and infant acute leukemia remain one of the most puzzling clinical issues in pediatric hematology-oncology. There is a paucity of studies focused on these rare, aggressive, acute leukemias; specifically, there is little study on the differences in disease in the youngest of infants less than 1 year of age unlike the numerous studies of the disease in older children. The United States National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer population registry program has been integral for a plethora of clinical population and pathology research studies for numerous diseases in the last 40 years and has an excellent resource for investigation of the infant population. Laboratory medicine and pathology professionals must use pathology results not only to diagnose individuals after the disease has been discovered, but the information must be applied retrospectively to develop new testing strategies. By classifying the intense heterogeneity within these cancers, the distinct changes of the diseases within individuals can be established, ultimately reshaping diagnostic methodologies. Through the application of Integrative Molecular Pathological Epidemiology to a 325-infant case series from the SEER program from 2008 to 2014, this dissertation study was used to evolve the classification of these pediatric cancers with the application of scientific nosology. This dissertation study has documented characteristics of this population for application in further precision medicine investigations to influence laboratory medicine algorithms for diagnosis and management of patients guiding health policy that are aimed at improving outcomes in the youngest of children. Acknowledgement I would like to extend a sincere thank you to the many people across the globe who so generously contributed to the work presented in this thesis. Profound gratitude goes to my mentor, Akiva Turner. My PhD has been an amazing experience, and I thank Akiva wholeheartedly not only for his tremendous academic support but also for giving me the opportunity to become an independent researcher. Not many PhDs provide the ability and flexibility to co-direct a clinical genetics laboratory in another country while exploring the cancer registry genetics data in another! Similarly, profound gratitude goes to C. Lynn Chevalier and Debra A. Dixon who have been dedicated committee members unwavering in their commitment to share their expertise so willingly. Thank you to the faculty and staff of the Dr. Pallavi Patel College of Health Care Sciences at Nova Southeastern University who helped me achieve my educational goals. To my friends and colleagues, thank you for listening, offering me advice, and supporting me through this entire process. Thanks go to Mom and Dad for always being there and encouraging me to embark on the science path. I am particularly indebted to my great-grandmother Idella for her constant faith in my early education. To Annie, I thank her for her untiring support and guidance throughout my journey. Finally, but by no means least, thanks go to J. T., Mikayla, and Gwendolyn for their incredulous support. They are the most important people in my world, and who were always there to remind me “You jump; I jump, remember?” I dedicate this thesis to them. Table of Contents Page Abstract .......................................................................................................................................... iii Acknowledgement ......................................................................................................................... iv Table of Contents ............................................................................................................................ v List of Tables ................................................................................................................................ vii List of Figures ................................................................................................................................. x Chapter 1: Introduction ................................................................................................................... 1 Introduction to the Chapter ....................................................................................................... 1 Background to the Problem ...................................................................................................... 3 Statement of the Problem .......................................................................................................... 7 Relevance ................................................................................................................................ 10 Elements .................................................................................................................................. 12 Theories............................................................................................................................. 12 Research Questions ................................................................................................................. 21 Hypotheses ........................................................................................................................ 23 Definitions of Terms ............................................................................................................... 23 Description of Variables ......................................................................................................... 25 Rationale ................................................................................................................................. 27 Assumptions ............................................................................................................................ 27 Summary of the Chapter ......................................................................................................... 28 Chapter 2: Review of the Literature .............................................................................................. 29 Introduction to the Chapter ..................................................................................................... 29 Historical Overview .........................................................................................................

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