Pathogenesis of early leukemia and lymphoma

Issue title: Translational Pathology of Early Cancer

Guest editors: Sudhir Srivastavax and William E. Grizzley

Article type: Research Article

Authors: Zhao, X. Frank^a | Reitz, Marvin^b | Chen, Qing Ching^a | Stass, Sanford^{a; *}

Affiliations: [a] Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA | [b] Department of Medicine, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA | [x] Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA | [y] Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: [*] Corresponding author: Sanford A. Stass, MD, Chair, Department of Pathology, Chair, Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore, MD, USA. E-mail: [email protected].

Abstract: In the past several decades, great progress has been made in our understanding of normal hematopoiesis and its malignant transformation. This article provides a comprehensive and up-to-date review of pathogenesis of leukemia and lymphoma, with an emphasis on early molecular events. Current concepts of normal hematopoiesis and its key regulatory processes are summarized. Various environmental and infectious factors that play a causative role in hematopoietic malignancies are described. In particular, several causative viruses, i.e. HTLV1, HHV8 and EBV, are discussed in depth. Numerous genetic abnormalities have been identified in leukemia and lymphoma, including chromosomal translocations, gene deletions, amplifications, and point mutations. Synopses are included for the most frequently encountered aberrations, and their relation to normal and malignant hematopoiesis, disease classification and prognosis. Major molecular mechanisms and signal transduction pathways involved in the leukemogenesis are depicted; these include blockage of differentiation, self-sustainable proliferation, abnormal cell cycle progression and impaired apoptosis. Also included are the recently discovered microRNAs, and their potential role in the pathogenesis of leukemia and lymphoma. Future directions in leukemia and lymphoma research are presented, including several modern molecular technologies and their importance in developing new biomarkers for early detection of leukemia and lymphoma.

Keywords: Leukemia, lymphoma, hematopoiesis, stem cells, pathogenesis, leukemogenesis, chromosomal translocation, Philadelphia chromosome, oncogene, tumor suppressor, microRNA, retrovirus, herpes virus, acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloproliferative neoplasm, gene expressing profiling

DOI: 10.3233/CBM-2011-0178

Journal: Cancer Biomarkers, vol. 9, no. 1-6, pp. 341-374, 2011