134 Curr Hematol Malig Rep (2012) 7:133–143 Fig. 1 Next-generation sequencing (NGS) in B/T ALL. Whole ge- nome/exome/transcriptome sequencing approaches provide a compre- hensive view of the landscape of genetic alterations in leukemia allowing the identification of potential novel markers for diagnosis, risk-stratification, and tailored treatments. Here, studies using NGS approaches in B/T ALL are schematized & & & & B-Progenitor Acute Lymphoblastic Leukemia Prognostic Factors Based on Cytogenetics Cytogenetics and fluorescence in situ hybridization (FISH) reveal recurring chromosome abnormalities, including numer- ical and structural changes, in approximately 80 % of ALL. Substantial differences in the frequencies of some recurring abnormalities are present between children and adults. The t(8;14)[MYC-IgH], present in a high proportion of Burkitt cell leukemia/lymphoma, occurs in approximately 1 % of adults. This translocation is associated with French-American-British (FAB)-L3-type leukemia cells, high incidence of central nervous system involvement at diagnosis, and poor prognosis [6]. The t(4;11)[MLL-AF4] is present in up to 60 % of infants younger than 12 months, but is rarely observed in adult patients. This translocation is associated with FAB L1 or L2 morphology, immature immunopheno- type, B-cell lineage, frequent co-expression of myeloid antigens, and high leukocyte counts. The prognosis is poor in both adults and children [7, 8]. The t(9;22)[BCR-ABL1] that produces the Philadelphia (Ph) chromosome is observed in about 2 % to 5 % of children and 30 % of adults. This translocation is associ- ated with a dismal prognosis. Treatment with tyrosine kinase inhibitors (TKIs) has produced promising results, although with the passage of time, problems have emerged with drug resistance and disease persistence [9]. The t(1;19)[TCF3-PBX1] occurs in approximately 30 % of pre-B cell childhood ALL patients. In the past, patients with the t(1;19) typically had early treatment failure. However, this adverse prognosis can be & & & overcome by more intensive chemotherapy such that the t(1;19) is now associated with a favorable prognosis [10, 11]. The t(12;21)[ETV6-RUNX1] is detectable by FISH or polymerase chain reaction analysis in about 25 % of children and 3 % of adults with B-ALL. Patients gener- ally have a favorable prognosis [12]. Patients with hyperdiploidy with more than 50 chromo- somes often have a good prognosis. The individual structural abnormalities do not appear to influence outcome in patients with hyperdiploidy except for the t(9;22), which is associated with a poor progno- sis [13]. Approximately 5 % to 6 % of ALL patients, independent of age, have clonal loss of various chromosomes, resulting in a hypodiploid clone with fewer than 46 chromosomes. These patients generally have a poor prognosis, especially those with near-haploid and low-hypodiploid clones. Similarly, deletion of 9p is an unfavorable risk factor associated with a high rate of relapse in B-precursor ALL in children [14]. Prognostic Factors Based on Genomic Profiling The advent of high-resolution genome-wide analyses of gene expression, DNA copy number alterations (CNA), and loss of heterozygosity have led to the detection of many novel genetic abnormalities refining the prognostic models for ALL (Table 1). Using single nucleotide polymorphism (SNP) arrays, many groups detected multiple submicroscopic CNA not evident on cytogenetic analysis, commonly less than one megabase (Mb) in size and targeting, in most of the cases, a single or few genes implicated in key cellular pathways,