Immunophenotyping as biomarker platform in acute leukemia

Abstract

In the past two decades, scientific advances have yielded new insights into the genetic and biological features of acute leukemia. Despite these advances, the mortality rate of patients with acute leukemia is still high. Over the same time period, flow cytometric immunophenotyping has become a major tool in current clinical practice for the diagnosis and classification of acute leukemia and the detection of residual leukemic cells after chemotherapy. However, the identification of patients with a high risk of relapse following therapy through the detection of leukemic minimal residual disease (MRD) remains a major challenge since it is difficult to identify small numbers of residual leukemic blasts in a background of nonmalignant regenerating bone marrow cells. The detection of leukemic blasts rests on the identification of characteristic immunophenotypic aberrancies by flow cytometry that allow discrimination from normal hematopoietic cells. Unfortunately, the immunophenotype of leukemic blasts often closely resembles their normal counterparts in regenerating bone marrows after cytotoxic chemotherapy which makes definitive assessment of leukemic MRD difficult. Emerging molecular analyses such as mRNA profiling by DNA microarray and proteomic analysis by mass spectrometry have been employed to identify new biomarkers of leukemic MRD. Despite these advanced methods, few new biomarkers of leukemic blasts are available clinically which hinders the assessment of leukemic MRD. One way to overcome this barrier is to develop new molecular probes and to discover new biomarkers, which can be used in flow cytometric analysis to distinguish leukemia cells from their normal counterparts.