PROM-1 (CD 133) overexpression in adult acute lymphoblastic leukemia Egyptian patients and relation to outcome

Abstract

Acute lymphoblastic leukemia is a type of leukemia which is characterized by 20% or more lymphoblasts in the bone marrow and/or the blood. It is a rapidly developing, abnormal growth of the cells that are precursors of lymphoblasts. The peak incidence occurs between age 2 and 5 years. The most frequent signs are lymphadenopathies, hepatosplenomegaly, fever, anemia, signs of hemorrhage, and bone tenderness. Biological findings include hyperleukocytosis due to circulating lymphoblasts. Most of the cases of acute lymphoblastic leukemia show chromosomal and genetic abnormalities. Prominin-1, a pentaspan transmembrane protein, is a unique cell surface marker commonly used to identify stem cells, including endothelial progenitor cells and cancer stem cells. However, recent studies have shown that prominin-1 expression is not restricted to stem cells but also occurs in modified forms in many mature adult human cells. prominin-1 plays an active role in cell growth through its ability to interact and potentiate the antiapoptotic and pro-angiogenic activities of vascular endothelial growth factor. Additionally, prominin-1 promotes tumor growth by supporting angiogenesis and inhibiting tumor cell apoptosis. Prominin-1 expression has been associated with a wide array of cancer types including hematopoietic malignancies such as acute lymphocytic leukemia, chronic lymphocytic leukemia and myelodysplastic syndrome. PROM1/CD133 is similarly expressed between MLLr B-cell ALL primary blasts and normal non-lymphoid HSPCs across ontogeny, thus indicating that “on-target, off-tumor” toxic/myeloablative effects are likely to occur if used in a bi-specific CAR approach where CD133 antigen will be constantly targeted regardless of the co-expression of CD19 in the same cell. Our data therefore raises concerns about using CD133 as a target for MLLr B-cell ALL immunotherapy.