In recent years, the panel of known molecular mutations in acute lymphoblastic 
leukemia (ALL) has been continuously increased. In Philadelphia-positive ALL, 
deletions of the IKZF1 gene were identified as prognostically adverse factors. 
These improved insights in the molecular background and the clinical 
heterogeneity of distinct cytogenetic subgroups may allow most differentiated 
therapeutic decisions, for example, with respect to the indication to allogeneic 
HSCT within genetically defined ALL subtypes. Quantitative real-time PCR allows 
highly sensitive monitoring of the minimal residual disease (MRD) load, either 
based on reciprocal gene fusions or immune gene rearrangements. Molecular 
diagnostics provided the basis for targeted therapy concepts, for example, 
combining the tyrosine kinase inhibitor imatinib with chemotherapy in patients 
with Philadelphia-positive ALL. Screening for BCR-ABL1 mutations in 
Philadelphia-positive ALL allows to identify patients who may benefit from 
second-generation tyrosine kinase inhibitors or from novel compounds targeting 
the T315I mutation. Considering the central role of the molecular techniques for 
the management of patients with ALL, efforts should be made to facilitate and 
harmonize immunophenotyping, cytogenetics, and molecular mutation screening. 
Furthermore, the potential of high-throughput sequencing should be evaluated for 
diagnosis and follow-up of patients with B-lineage ALL.