Abstract
The diagnosis of acute lymphoblastic leukemia (ALL) is made by evaluating morphology and immunophenotype. However, appropriate risk stratification and decisions regarding the intensity of therapy are influenced by additional clinical and laboratory testing that reflect the biology of the disease. Recent years have seen tremendous progress in uncovering genetic lesions that influence the biology of ALL. In recognition of these advances, the 2008 WHO classification incorporated the category of B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities into the classification of precursor lymphoid neoplasms. Based on the knowledge available at the time, genetic lesions associated with distinct clinical features, immunophenotype, prognosis, or other unique biological characteristics were included in this category. Not surprisingly, significant novel genetic lesions that profoundly affect the biology of ALL have since been identified and will have a major impact on risk stratification and may ultimately be incorporated into future classification schemes. After establishing an initial diagnosis and treatment regimen, hematopathologists must also evaluate for minimal residual disease (MRD) to determine the need for additional intervention because MRD remains the most useful clinical indicator of disease progression and response to treatment. Doing so requires familiarity with not only morphology, but also flow cytometry and molecular genetics. Although not all of these applications are handled directly by the hematopathologist, it is our strong belief that meaningful involvement in patient care dictates that hematopathologists appreciate all aspects of ALL diagnosis and disease monitoring. This review covers the salient aspects of recent advances in the biology of ALL and evaluation of MRD, placing emphasis on how this information may ultimately be used to improve risk stratification and, as a result, patient outcomes.