Special Issue "Leukemia Arising from Chemical Exposures and Chemotherapeutic Drugs"

Guest Editor
Dr. Luoping Zhang
Division of Environmental Health Sciences, School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA
Website: http://sph.berkeley.edu/faculty/zhang.php
E-Mail: luoping@berkeley.edu
Phone: +1 510 643 5189
Fax: +1 510 642 0427
Interests: the impact and mechanisms of exposures to toxic chemicals on human health, particularly in carcinogenesis and leukemogenesis; application of omic technologies in molecular epidemiological studies; and the development of new tools and assays to explore relevant biomakers

Dear Colleagues,

The etiology of the blood cancer leukemia is still largely unknown; however, exposures to toxic chemicals and cancer-therapeutic drugs can cause leukemia in adults and children. Benzene is a well established leukemogen and occupational exposure to formaldehyde has recently been shown to increase leukemia risk. Additionally, a portion of primary cancer patients develop acute myeloid leukemia (AML) after treatment with chemotherapeutic drugs, such as alkylating agents (melphalan etc) and DNA topoisomerase II (Topo II) inhibitors (etoposide etc.). Evidence suggests that the leukemia associated with exposure to different types of leukemogen exhibits specific molecular changes. For instance, therapy-related AML resulting from treatment with alkylating agents is mainly associated with loss of chromosomes 5 and 7, while Topo II inhibitor-induced AML is commonly associated with chromosomal translocations. Although chromosomal aneuploidy and rearrangements are hallmarks of leukemia, it is not well understood how these chemicals interact with normal hematopoietic stem/progenitor cells and disrupt bone marrow niches. This special issue will focus on molecular (genetic and epigenetic) mechanisms of chemically-induced leukmogenesis in exposed humans, experimental animal models and in vitro systems. We will accept original research reports, short communications/commentaries, and limited review papers deemed relevant.

Dr. Luoping Zhang
Guest Editor

Submission

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• Leukemogenesis
• Leukemogen
• Benzene
• Formaldehyde
• Therapy-related leukemia
• Alkylating agents
• DNA topoisomerase II inhibitors
• Mechanisms

Type of Paper: Article
Title: The Aryl Hydrocarbon Receptor Pathway: A Key Component of the miRNA-Mediated AML Signalisome
Auhtors: Julia E. Rager¹ and Rebecca C. Fry^{1,2
Affiliation: 1} Department of Environmental Sciences and Engineering, Gillings School of Global Public Health
² Curriculum in Toxicology, University of North Carolina - Chapel Hill, Chapel Hill, North Carolina, USA
Abstract: Recent research has spotlighted the role of microRNAs (miRNAs) as critical epigenetic regulators of hematopoietic stem cell differentiation and leukemia development. Despite the recent advances in knowledge surrounding epigenetics and leukemia, the mechanisms underlying miRNAs’ influence on leukemia development have yet to be clearly elucidated. Our aim was to identify high ranking biological pathways altered at the gene expression level and under epigenetic control. Specifically, we set out to test the hypothesis that miRNAs dysregulated in acute myeloid leukemia (AML) converge on a common pathway that can influence signaling related to hematopoiesis and leukemia development. We identified genes altered in AML patients that are under common regulation of seven key miRNAs. By mapping these genes to a global interaction network, we identified the “AML Signalisome”. The AML Signalisome comprises 53 AML-associated molecules, and is enriched for proteins that play a role in the aryl hydrocarbon receptor (AhR) pathway, a major regulator of hematopoiesis. Furthermore, we show biological enrichment for hematopoiesis-related proteins within the AML Signalisome. These findings provide insight into the pathophysiological mechanisms underlying leukemogenesis, and may help to prioritize targeted pathways for disease prevention and treatment.
Keywords: aryl hydrocarbon receptor; gene expression; leukemia; microRNA; systems biology