Acute Lymphoblastic Leukemia

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Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and it is characterized by uncontrolled growth and impaired differentiation of lymphoblasts. Although ALL is a heterogeneous disease, there are two major subtypes that are characterized by the type of leukemic cells present; either B cells (B-ALL) or T cells (T-ALL). Some instances of ALL are characterized by the presence of the Philadelphia chromosome, a specific translocation resulting in the fusion gene, BCR-ABL. The BCR-ABL fusion protein is a constitutively active tyrosine kinase that accelerates cell division while inhibiting DNA repair mechanisms. Other chromosomal alterations and activating point mutations leading to misregulated Notch signaling have also been associated with ALL.

Following chemotherapy, immunophenotyping can be a useful strategy to monitor minimal residual disease (MRD) or the presence of remaining leukemic stem cells. Successful MRD analysis must distinguish normal, CD19+Neprilysin+, B cells or CD3+ T cell progenitors from leukemic cells. Cytoplasmic CD3 localization has been used to identify T-ALL cells, and Siglec-2 is a B-ALL cell surface antigen. The identification of additional putative leukemic stem cell markers, such as CTNNA1, may also inform targeted therapeutic development.