Evaluation of ADAM28 expression in adult Egyptian Acute Myeloid Leukemia patients and its impact on outcome

Abstract

cute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is fatal as a result of primary refractoriness, relapse, or treatment-related mortality. Although the majority of patients with AML enter remission upon induction chemotherapy, the risk of relapse is considerable. Transplantation regimens can be curative, but it remains challenging to identify high risk patients suitable for early transplantation. The current risk assignment uses age, genetic subtype and response to initial therapy to stratify patients. Notably, many relapses occur in patients who initially present with favorable prognostic features. New prognostic biomarkers may fine-tune risk assessment in adult AML and understanding their roles in leukemia may facilitate the selection of treatment options and benefit patients. Therefore, there is a clear need to improve the identification of patients at increased risk of relapse, particularly those currently stratified as favorable risk, for whom more intensive treatments are already available. ADAM28 is a member of the ADAM (a disintegrin and metalloproteinase) gene family and consists of two isoforms, prototype membrane-type form and short secreted form. The metalloproteinase domain of ADAM28 has the zinc binding consensus sequence, and ADAM28 exhibits catalytic activity to a few substrates such as insulin-like growth factor binding protein-3. ADAM28 in malignant cells is up-regulated by multiple mechanisms, including the cleavage of von Will brand factor (vWF), insulin-like growth factor binding protein-3 (IGFBP-3) and connective tissue growth factor (CTGF), as well as the promoting PSGL-1/P-selectin-mediated cell adhesion. Studies show that ADAM28 is highly expressed in several human tumors, such as lung, breast and bladder cancers, and chronic lymphocytic leukemia, and its tissue expression levels correlate with cancer metastasis.