REVIEW Relapse of Acute Lymphoblastic Leukemia in Children in the Context of Microarray Analyses Joanna Szczepanek • Jan Styczyn ´ski • Olga Haus • Andrzej Tretyn • Mariusz Wysocki Received: 19 April 2010 / Accepted: 19 August 2010 / Published online: 19 January 2011 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2011 Abstract Over the last four decades the treatment of patients with newly diagnosed childhood acute lympho- blastic leukemia (ALL) has improved remarkably. However, still about 20% of children with ALL relapse despite risk-adapted polychemotherapy. The prognosis of relapsed ALL is relatively poor, even with modern aggres- sive chemotherapy. Identification of the biological and genetic mechanisms contributing to recurrence in patients with ALL is critical for the development of effective ther- apeutic strategies to treat refractory leukemic patients. Allogeneic hematopoietic stem-cell transplantation is the treatment of choice for many children with relapsed ALL. The gene expression profile obtained by microarray tech- nology could provide important determinants of the drug response and clinical outcome in childhood ALL. Incorpo- ration of the data on expression levels of newly identified genes into existing strategies of risk stratification might improve clinical management. Current microarray data show correlation of in vitro drug resistance with significant patterns of gene expression and explain clinical differences between early and late relapse. Genes involved in cell proliferation, self-renewal and differentiation, protein bio- synthesis, carbohydrate metabolism, and DNA replication and repair are usually among those highly expressed in relapsed lymphoblasts. Current status and future perspec- tives of microarray data on gene expression and drug resistance profile in relapsed pediatric ALL are discussed in this review. Keywords Gene expression profile Á Copy number abnormalities Á Microarray Á Children Á Acute lymphoblastic leukemia Á Relapse Introduction Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with an incidence of 30.9 cases/ million children/year (Gaynon et al. 1998; Pui and Jeha 2007). With contemporary treatment based on systemic combination chemotherapy and specific preventive therapy of the central nervous system (CNS), about 98% of chil- dren with ALL experience complete remission (Holleman et al. 2004; Pui et al. 2001, 2004; Pui and Evans 1998). This improved outcome is also related to stratification of individual patients into risk groups based on prognostic factors incorporating age, immunophenotype, white blood cell (WBC) count, CNS involvement, response to therapy and genetic findings. However, still about 20–25% of newly diagnosed patients subsequently experience leuke- mic recurrence, with bone marrow (BM) being the most common site of disease relapse. Pediatric relapsed ALL is a more frequent disease than non-Hodgkin lymphoma, Wilms tumor, Hodgkin disease or acute myeloid leukemia (Gaynon et al. 1998). J. Szczepanek Á J. Styczyn ´ski (&) Á M. Wysocki Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Curie-Sklodowskiej 9, 85-094 Bydgoszcz, Poland e-mail: jstyczynski@cm.umk.pl J. Szczepanek Á A. Tretyn Department of Biotechnology, Institute of Molecular Biology, Nicolaus Copernicus University, Torun ´, Poland O. Haus Department of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland Arch. Immunol. Ther. Exp. (2011) 59:61–68 DOI 10.1007/s00005-010-0110-1 123