Curr Hematol Malig Rep (2012) 7:133–143 DOI 10.1007/s11899-012-0122-5 ACUTE LYMPHOCYTIC LEUKEMIA (F RAVANDI, SECTION EDITOR) Cytogenetic and Molecular Predictors of Outcome in Acute Lymphocytic Leukemia: Recent Developments Ilaria Iacobucci & Cristina Papayannidis & Annalisa Lonetti & Anna Ferrari & Michele Baccarani & Giovanni Martinelli Published online: 20 April 2012 # The Author(s) 2012. This article is published with open access at Springerlink.com Abstract During the last decade a tremendous technologic progress based on genome-wide profiling of genetic aberra- tions, structural DNA alterations, and sequence variations has allowed a better understanding of the molecular basis of pediatric and adult B/T- acute lymphoblastic leukemia (ALL), contributing to a better recognition of the biological heterogeneity of ALL and to a more precise definition of risk factors. Importantly, these advances identified novel potential targets for therapeutic intervention. This review will be focused on the cytogenetic/molecular advances in pediatric and adult ALL based on recently published articles. Keywords ALL . Acute lymphoblastic leukemia . SNP array . Next generation sequencing Introduction ALL represents a biologically and clinically heteroge- neous group of B/T-precursor-stage lymphoid cell ma- lignancies arising from genetic insults that block lymphoid differentiation and drive aberrant cell I. Iacobucci (*) : C. Papayannidis : A. Ferrari : M. Baccarani : G. Martinelli Department of Hematology and Oncological Sciences “L. and A. Seràgnoli”, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy e-mail: ilaria.iacobucci2@unibo.it A. Lonetti Department of Human Anatomy, University of Bologna, Cellular Signalling Laboratory, Bologna, Italy proliferation and survival. Incidence and cure rates dif- fer among children and adults. In children, ALL is the commonest malignancy accounting for approximately 25 % of childhood cancer and it has 5-year event-free survival rates ranging between 76 % and 86 % in patients receiving protocol-based therapy. In adults, ALL is less common and generally carries a worse prognosis with a long-term survival probability less than 35–40 % [1, 2]. Although there is remarkable progress made in the treatment of ALL in children and, with less efficacy, in adults, several ALL subtypes continue to have a poor prognosis and in a proportion of long- term surviving patients, treatment is responsible for short and long-term toxicities. Consequently, there is a need in improving the molecular dissection of subtypes, identifying genetic alterations that predict the risk of treatment failure, and developing novel and targeted therapies. Cytogenetics has long been used for diagno- sis, risk stratification, and therapeutic implications, how- ever experimental models [3, 4] have established that primary cytogenetic abnormalities alone are insufficient to induce leukemia and that cooperative mutations are required. The development of microarray technologies to profile gene expression and structural genetic alterations in a genome-wide and high-resolution fashion have rev- olutionized our ability to identify genetic abnormalities providing important insights into the pathways deregu- lated in ALL [5]. Moreover, recently the development of next-generation sequencing (NGS) technologies has provided researchers with completely new and effective tools for the discovery of novel alterations, depicting an exhaustive picture of the leukemia genome complexity (Fig. 1). This review emphasizes the most important and newest findings obtained from genomic analysis of B/T- lineage ALL.