The Insulin-like Growth Factor System in Hematopoietic Cells

Abstract

The insulin-like growth factor (IGF) system regulates proliferation and differentiation of hematopoietic cells. IGFs exert their effects through specific receptors on growing and differentiating blood cells as they emerge from their small pool of ancestral stem cells. The IGF system is complex as both stimulating and inhibiting effects occur by interaction of IGFs and IGF-binding proteins (IGFBPs). IGFs stimulate erythrocytes and lymphocytes but also promote leukemic hematopoietic cell proliferation. IGF-I appears to be correlated with hemoglobin levels in anemia and could also be of benefit for patients with bone marrow aplasia after transplantation. Hypersensitivity to IGF-I has been implicated as an underlying cause of polycythemia vera. Loss of imprinting of IGF-II is found in acute myeloid leukemia and myelodysplastic syndrome. Apoptosis of hematopoietic cells is significantly reduced by IGF-I involving an intriguing signal transduction pathway. IGFs could therefore, although not classical hematopoietic growth factors, be of benefit for patients with diverse hematopoietic disorders.

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures

“…33,34 IGF-1 is a mediator of the action of growth hormone on normal tissues and it performs multiple functions, including cell proliferation and inhibition of apoptosis in hematopoietic cells. 35 The similarity in the expression profiles of AGM cells and C17.2 is in line with recent proposals on the close relationship between hematopoiesis and neuropoiesis during embryonic development and in the manifestation of 'adult stem cell plasticity'. [36][37][38] The overlapping genetic programs of the two systems could imply that a reciprocal regulatory mechanism might be in place.…”

Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves’ Disease May Carry Functional Consequences for Disease Pathogenesis

“…2). This expression is retained by peripheral erythrocytes, monocytes, and NK cells (7). IGF-1R is also strongly expressed on T cells within the marrow but not by the majority of control mature T cells (Fig.…”

“…IGF-1 and IGF-1R play important roles in hemopoietic cell growth and differentiation and normal immune function (7). Peripheral blood T and B cells and monocytes from control human donors express low levels of IGF-1R in vivo (8,9).…”

Bcr-Abl induces autocrine IGF-1 signaling

“…The importance of IGF-1 signaling in hematopoiesis (Akahane et al, 1987;Kurtz et al, 1988;Merchav et al, 1988a, b;Sanders et al, 1993;Zumkeller and Burdach, 1999) suggests that deregulation of IGF-1 expression may play a role in the CP to BC transition. IGF-1 is also important in leukemogenesis as seen by its ability to stimulate myeloid and lymphoid cells in culture (Johnson et al, 1992;Schwartz et al, 1996), to stimulate proliferation of CML BC cell lines (Hizuka et al, 1987), to increase bone marrow blast colony formation in patients with acute myeloid leukemia (AML; Zadik et al, 1993) and to promote growth of AML blasts (Doepfner et al, 2007).…”