Granulocyte colony-stimulating factor and leukemogenesis

Mediators of Inflammation
Lorena Lobo de FigueiredoEduardo Magalhães Rego

Abstract

The granulocyte colony-stimulating factor (G-CSF) plays an important role in normal granulopoiesis. Its functions are mediated by specific receptors on the surface of responsive cells and, upon ligand binding, several cytoplasmic tyrosine kinases are activated. The cytoplasmic region proximal to the membrane of the G-CSF receptor (G-CSF-R) transduces proliferative and survival signals, whereas the distal carboxy-terminal region transduces maturation signals and suppresses the receptor's proliferative signals. Mutations in the G-CSF-R gene resulting in truncation of the carboxy-terminal region have been detected in a subset of patients with severe congenital neutropenia who developed acute myelogenous leukemia (AML). In addition, the AML1-ETO fusion protein, expressed in leukemic cells harboring the t(8;21), disrupt the physiological function of transcription factors such as C/EBPalpha and C/EBPepsilon, which in turn deregulate G-CSF-R expression. The resulting high levels of G-CSF-R and G-CSF-dependent cell proliferation may be associated with pathogenesis of AML with t(8;21). Moreover, in vitro and in vivo studies demonstrated that G-CSF may act as a co-stimulus augmenting the response of PML-RARalpha acute promyelocytic leuke...Continue Reading

References

Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R FukunagaS Nagata
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·W Wiktor-JedrzejczakE R Stanley
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·E StanleyA R Dunn
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·D E ZhangD G Tenen
Feb 15, 2001·Seminars in Hematology·E M Rego, P P Pandolfi
Mar 29, 2002·The Hematology Journal : the Official Journal of the European Haematology Association·N Da SilvaC Chomienne
Jul 20, 2002·Trends in Molecular Medicine·Eduardo M Rego, Pier Paolo Pandolfi
Feb 4, 2003·Nature Reviews. Cancer·Daniel G Tenen
May 24, 2003·Experimental Hematology·Andrew A G AprikyanDavid C Dale
May 24, 2003·The Hematology Journal : the Official Journal of the European Haematology Association·Felicetto FerraraLuigi Del Vecchio
Aug 22, 2003·The New England Journal of Medicine·Bob LöwenbergUNKNOWN Swiss Group for Clinical Cancer Research

❮ Previous
Next ❯

Related Concepts

Related Feeds

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.