New Markers for Minimal Residual Disease in Acute Lymphoblastic Leukemia

Overview

Acute lymphoblastic leukemia , also known as acute lymphocytic leukemia, characterized by the overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblasts, causing damage and death by inhibiting the production of normal cells (such as red and white blood cells and platelets) in the bone marrow and by spreading (infiltrating) to other organs. Acute lymphoblastic leukemia is most common in childhood, with a peak incidence at 2-5 years of age and another peak in old age.

In recent years, new pieces of information obtained through immunophenotyping, cytogenetics and genomic profiling. Chemotherapy resistance have contributed to a better understanding of the pathology of this complex disorder and to recognition of subgroups of patients who respond differently to therapy. The possible impact of the expression of various markers has been studied in ALL. In patients with acute leukemia, treatment decisions are based on the status of peripheral blood and bone marrow cellularity. This provides a measure of the efficacy of therapy and can reveal leukemia relapse. The reliability of morphologic examination of peripheral blood and bone marrow largely depends on the hematologist's expertise, and its sensitivity is fundamentally limited by the similarities in appearance between leukemic cells and normal lympho-hematopoietic progenitors. Therefore, patients in complete morphologic remission may still have a large number of residual leukemic cells (potentially up to 1010). Minimal residual disease (MRD) is currently the most powerful prognostic indicator in Precursor B acute lymphoblastic leukemia (B ALL). MRD analysis can be done by either flow cytometric or molecular techniques. Flow cytometric detection holds potential for wider applicability than molecular techniques because flow cytometric methods for leukemia diagnosis are already established at most cancer centers worldwide. Flow cytometric detection of MRD is based on the principle that ALL cells express immunophenotypic features that can be used to distinguish them from normal hematopoietic cells, including hematogones and activated lymphocytes commonly referred to as Leukemia associated immunophenotype (LAIP). In virtually all patients with ALL, leukemia-associated immunophenotypes can be defined at diagnosis and then used to monitor MRD during treatment. The reliability of flow cytometric MRD assays depends on several factors. The most important being the correct marker combination in use. Applicability is limited in some cases by the lack of suitable leukemia associated immunophenotype (LAIP) with the currently used markers and also antigen immunomodulation post treatment. Therefore, the identification of new leukemia markers that are easily detectable and are stably expressed in a large proportion of ALL cases should simplify the application of MRD studies, help extend their benefit to all patients and possibly enhance the sensitivity of MRD detection.

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