Preface

T-cell leukemia is relativelyrare malignancyof thymocytes. There are around 20 entities and variants of this disease. Each of them has different characteristics, including pathogenesis, epidemiology, diagnosis, therapeutic approaches, andprognosis. Although T-cell leukemia is relatively rare malignancy, many types of T-cell leukemiasstill havea very poor prognosis‐ due to rapid progression. Therefore, development of novel therapeutic and preventive strat‐ egies is necessary to improve prognosis. The purpose of this book entitled "T-Cell Leukemia - Characteristics, Treatment and Prevention"is to provide a comprehensive overview of the disease from the basics of pathogenesis, epidemiology, morphology, and immunological features. This book also highlights the most recent achievements from basic and clinical re‐ search including molecular mechanisms and novel therapies of T-cell leukemia.

The present book features contributions from international authors in various clinical and research fields of T-cell leukemia.The first chapter, "Molecular Pathogenesis of T-Cell leuke‐ mia" by Drs. Michael Litt, Bhavita Patel, Ying Li Yi Qiu and Suming Huang, provides an overview of molecular changesassociated withpathogenesisof T-cell acute leukemia (T-ALL).Specifically, chromosomal translocations which involve rearrangement of T-cell recep‐ tors and gene mutations which deregulate importantsignaling pathways involved in T-cell leukemogenesisare described. The second chapter, "Monoclonal Antibody Therapy of T-cell Leukemia and Lymphoma"writtenby Drs. TahirLatif, and John C. Morris, focuses on the current status of monoclonal antibody therapy of T-cell leukemia and lymphoma.A number of antibodies, including anti-CD2, anti-CD3, anti-CD4, anti-CD5, anti-CD25, anti-CD30, anti-CD52, anti-CD122, and anti-CCR4, which are currently studied for antibody therapy of Tcell leukemia and lymphoma are summarized.Chapter 3, "T- and NK/T-Cell Leukemia in East Asia"was written by Drs. Tsung-Hsien Lin, Yen-Chuan Hsieh, Sheng-Tsung Chang,and Shih-Sung Chuang.The countries in East Asia have higher relative frequencies of these types of leukemias and there are some differences in the clinical and pathological characteristics between Western and Asian countries.This chapter gives usan overview of clinico-patholog‐ ical analysis of various types of T- and NK/T-cell leukemias in the East Asia.

The next four chapters cover the topics of human T-cell leukemia virus type 1(HTLV-1) and adult T-cell leukemia/lymphoma (ATLL).Chapter 4, "Htlv-1-tax--all-roads-lead-to-transfor‐ mation" by Drs. Kendle Pryor and Susan J. Marriott, describes contribution of HTLV-1 viral protein Tax to transformation of HTLV-1 infected cells. In this chapter, cellular transforma‐ tion by Tax both in tissue culture and transgenic mouse models are summarized.The molec‐ ular mechanisms of Tax mediated transformation isalso described from several aspects, such as transcription factors, DNA repair pathways, and cell cycle regulation.Chapter 5,"Glycan Profiling Analysis of Adult T-cell Leukemia (ATL) Cells with the High Resolution Lectin Microarrays"is written by Drs. HidekatsuIha and Masao Yamada. Glycans have been con‐

sidered biomarkers of cancer. In this chapter, the evidences that glycan profiles are useful biomarker for diagnosis and prognosis ofATLL are discussed. Chapter 6, "Prevention of Hu‐ man T-Cell Lymphotropic Virus Infection and Adult T-Cell Leukemia", is written by Drs. Makoto Yoshimitsu, Tomohiro Kozako, NaomichiArima.Although many efforts to prevent infection of HTLV-1 have been made in many countries, about 20 million people are infected with HTLV-1 and ATLL is still developed among carriers. Understanding how to prevent HTLV-1 infection and treatment related diseases is still big issue in the world health. This chapter provides the overview of prevention and current treatment for ATLL not only from clinical but also from research aspects. The last chapter, Chapter 7, "The Roles of AMP-Acti‐ vated Protein Kinase-Related Kinase 5 as a Novel Therapeutic Target of Human T-cell Leu‐ kaemia Virus Type 1-Infected T-Cells" by Dr. Mariko Tomita was focused on ARK5, a fifth member of the AMP-activated protein kinases(AMPK) catalytic subunit family and ana‐ lyzed its role on the growth of HTLV-1-infected T-cells.The novel findings that ARK5 is a novel target of NF-κB andaccelerates the growth of HTLV-1-infected T-cells during glucose starvationare summarized.

As an editor of this book,I would like to acknowledge all of the authors for their significant dedication and excellent works. I also thank Ms. ViktorijaZgela and entireInTech editorial team for helping me to publish this book. This book addresses key issues of characteristics, treatment and prevention of T-cell leukemia. I hope thatthis book will helpto developbasic and clinical approaches for treatment and prevention of T-cell leukemia.

> **Mariko Tomita** University of the Ryukyus Japan

**Chapter 1**

**Molecular Morphogenesis of T-Cell Acute Leukemia**

Many molecular alterations are involved in the morphogenesis of T-cell acute leukemia (T-ALL), classified as lymphoblastic leukemia/lymphoma by the World Health Organization. T-ALL is a malignant disease of the thymocytes which accounts for approximately 15% of pediatric acute lymphoblastic leukemia (ALL) and 20-25% of adult ALL. Frequently, it presents with a high tumor load accompanied by rapid disease progression. About 30% of T-ALL cases relapse within the first two years following diagnosis with long term remission in 70-80% of children and 40% of adults [1]-[4]. This poor prognosis is a consequent of our insufficient knowledge of the molecular mechanisms underlying abnormal T-cell pathogenesis. Under‐ standing the abnormal molecular changes associated with T-ALL biology will provide us with the tools for better diagnosis and treatment of lymphoblastic leukemia. Recent improvements in genome-wide profiling methods have identified several genetic aberrations which are associated with T-ALL pathogenesis. For simplification these molecular changes can be separated into 4 different groups: chromosome aberrations, gene mutations, gene expression profiles, and epigenetic alterations. This chapter will discuss these molecular changes in depth.

The progenitors for T lymphocytes arise in the bone marrow as long-term repopulating hematopoietic stem cells (LT-HSCs) (Figure 1). These cells then differentiate, generating shortterm repopulating hematopoietic stem cells (ST-HSCs) and lymphoid-primed multipotent progenitor (LMPP)[5]-[7]. LMPPs, which migrate via the blood and a chemotaxis process to the thymus [8], phenotypically resemble early T-cell progenitors (ETP)[9],[10]. ETP cells, also called double negative 1 (DN1), are capable of differentiating into either T-cells or myeloid

> © 2013 Litt et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Michael Litt, Bhavita Patel, Ying Li, Yi Qiu and

Additional information is available at the end of the chapter

Suming Huang

**1. Introduction**

**2. T-cell development**

http://dx.doi.org/10.5772/55144
