Immunophenotypic Evaluation of IL-7R α in Acute Leukaemia

Overview

Acute leukemia is generally understood to be a neoplastic process that exerts a maturational block at a hematopoietic precursor cell level, accompanied by a proliferative drive of varying degree. The resulting accumulation of cells, most frequently in the marrow, causes the typical clinical picture, which includes marrow failure, tissue infiltration, organomegaly and on occasion, tumor masses. AL is broadly classified as acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) (1). Acute lymphoblastic leukemia is frequently diagnosed in children and young adults, with incidence peaks between 2 and 5 years of age (2), whereas AML is the most common acute type in adults (3). In addition to leukemia cells themselves, cells of the immune system are a fundamental component of the tumor microenvironment (TME), which often modify the TME to be more favorable to tumor development and progression through producing cytokines and mediators (4,5) . Interleukins / interleukin receptors interaction plays important roles in the antitumor immune response through mediating cell-cell communication in TME and is reported to be relevant to patient prognosis (6,7). As a member of the Interleukin family, Interleukin 7 (IL7) play vital roles in hematopoiesis and the development of T lymphocytes, as well as the inflammation, autoimmune diseases and hematological cancers. Its function is mediated by the IL7 R, which is a membrane receptor consisted of the specific IL7Ra chain (CD127) and IL-7Rγ chain (common gamma chain shared by the receptors for IL-2,-4,-9,-15, and-21) (8). It is thus not surprising that activation of IL-7 signalling is seen in the majority of T-ALLs and in some of the B cell precursor ALL (9,10). Consistent with the absolute requirement of IL-7 to human T cell development, most T-ALLs have been shown to respond to IL-7. Thus targeting IL-7 signaling might be a reasonable general approach for treatment of T-ALL, regardless the presence of activating mutations. (10)

Acute leukemia is generally understood to be a neoplastic process that exerts a maturational block at a hematopoietic precursor cell level, accompanied by a proliferative drive of varying degree. The resulting accumulation of cells, most frequently in the marrow, causes the typical clinical picture, which includes marrow failure, tissue infiltration, organomegaly and on occasion, tumor masses. AL is broadly classified as acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) (1). Acute lymphoblastic leukemia is frequently diagnosed in children and young adults, with incidence peaks between 2 and 5 years of age (2), whereas AML is the most common acute type in adults (3). In addition to leukemia cells themselves, cells of the immune system are a fundamental component of the tumor microenvironment (TME), which often modify the TME to be more favorable to tumor development and progression through producing cytokines and mediators (4,5) . Interleukins / interleukin receptors interaction plays important roles in the antitumor immune response through mediating cell-cell communication in TME and is reported to be relevant to patient prognosis (6,7). As a member of the Interleukin family, Interleukin 7 (IL7) play vital roles in hematopoiesis and the development of T lymphocytes, as well as the inflammation, autoimmune diseases and hematological cancers. Its function is mediated by the IL7 R, which is a membrane receptor consisted of the specific IL7Ra chain (CD127) and IL-7Rγ chain (common gamma chain shared by the receptors for IL-2,-4,-9,-15, and-21) (8). It is thus not surprising that activation of IL-7 signalling is seen in the majority of T-ALLs and in some of the B cell precursor ALL (9,10). Consistent with the absolute requirement of IL-7 to human T cell development, most T-ALLs have been shown to respond to IL-7. Thus targeting IL-7 signaling might be a reasonable general approach for treatment of T-ALL, regardless the presence of activating mutations. (10).