Many patients with acute myeloid leukemia (AML) share a mutation in a gene called IDH. A University of Colorado Cancer Center study shows that this IDH mutation may be the first domino in a chain that leads to a more aggressive form of the disease.
\n‘In fact, it\u2019s not IDH itself that causes the problem,’ says Dan Pollyea, MD, MS, investigator at the CU Cancer Center and assistant professor of haematologic oncology at the University of Colorado School of Medicine. Rather, the mutation in IDH leads to exponentially higher blood levels of a protein called 2-hydroxyglutarate. This protein ‘mucks up,’ as Pollyea says, other genes that in turn promote cancer or fail to inhibit its growth.
\nThe recent study shows that AML patients in remission who retain high levels of 2-hydroxyglutarate \u2013 due universally to IDH mutation \u2013 are much more likely to relapse than patients without similarly elevated levels.
\nThe chain of causation includes another couple links.
\n‘2-hydroxyglutarate reduces genes\u2019 ability to regulate themselves,’ says Pollyea. Over time genes accumulate gunk in the form of methylation \u2013 these methyl groups attach to silence parts of gene promoters, helping to decide which genes are and are not turned into proteins. Too much methylation is associated with many cancers, including AML. And 2-hydroxyglutarate turns off one of the body\u2019s methylation-regulating genes.
\nSo an IDH mutation leads to high 2-hydroxyglutarate, leads to bad gene regulation, leads to hypermethylation, leads to AML.
\nPollyea hopes to stop the first domino from falling by targeting IDH mutations. ‘Imagine screening for patients prospectively and then if they have the mutation, we could use something like an IDH inhibitor,’ Pollyea says. Turn off this mutation and doctors may be able to turn of the disease, or at least its most aggressive characteristics.
\nBut the genetic testing for IDH mutation is currently costly and time consuming. And so Pollyea hopes to identify patients with the IDH mutation by looking downstream \u2013 tests for blood-levels of 2-hydroxyglutarate being developed at the CU Cancer Center could determine the patients most likely to benefit from an IDH inhibitor.
\nFinally, Pollyea and colleagues including molecular biologist James DeGregori, PhD, are exploring novel ways to target the IDH mutation. ‘I think that even beyond the very real promise of IDH inhibitor drugs, this is a potential weak spot for AML that can be targeted in a number of ways,’ Pollyea says.\nUniversity of Colorado Cancer Center<\/link>\n","protected":false},"excerpt":{"rendered":"
Many patients with acute myeloid leukemia (AML) share a mutation in a gene called IDH. A University of Colorado Cancer Center study shows that this IDH mutation may be the first domino in a chain that leads to a more aggressive form of the disease. ‘In fact, it\u2019s not IDH itself that causes the problem,’ […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/2056"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=2056"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/2056\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=2056"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=2056"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=2056"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}