The human KRAS gene is one of many implicated in acute myeloid leukemia (see MIM:601626). The RAS proteins are GDP/GTP-binding proteins that act as intracellular signal transducers and are crucial players in many signaling networks affecting cell cycle progression, growth, migration, cytoskeletal changes, apoptosis, and senescence. Originally defined as oncogenes, the RAS GTPase family includes KRAS (MIM:190070), HRAS (MIM:190020), and NRAS (MIM:164790); mutations in these three genes are among the most common events in human cancers.
UAS constructs of the human Hsap\KRAS gene carrying the oncogenic variants G12V or G12D have been introduced into flies. Expression of the G12V variant in fly hemocytes has been used in this model of acute myeloid leukemia: assessed in third instar larvae, a dramatic increase (nearly 100-fold) in the number of circulating hemocytes is observed; in adults, this genotype is lethal (at 25 degrees C). Genetic and pharmaceutical modifiers of the lethal and hemocyte overproliferation phenotypes have been characterized.
[updated Dec. 2021 by FlyBase; FBrf0222196]
Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults; it is uncommon under age 40. (Most childhood leukemias are acute lymphocytic leukemia, ALL). AML affects myeloid cells, resulting in an abundance of abnormal immature cells within the blood-cell-producing bone marrow; normal hematopoietic processes become increasingly compromised. Persons with AML are more likely to have infections and have an increased risk of bleeding as the numbers of healthy blood cells decrease. [from MedlinePlus; https://www.nlm.nih.gov/medlineplus/ency/article/000542.htm ]
Mutations in one of the three canonical Ras GTPase genes, HRAS, NRAS, or KRAS, are among the most common events in human tumorigenesis (Fernandez-Medarde and Santos, 2011; pubmed:21779504).
The RAS proteins are members of a large superfamily of low-molecular-weight GTP-binding proteins. The RAS proteins control signalling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. Three members of the RAS family, HRAS, KRAS and NRAS, are found to be activated by mutation in human tumors. These three members are very closely related, having 85% amino acid sequence identity (Downward, 2003; pubmed:12509763).
Many to many: multiple related genes in both species.
