MD Anderson study identifies leukemia tumor suppressor
MD Anderson News Release September 24, 2015
Protein-coding gene hnRNP K may be culprit in acute myeloid leukemia
MD Anderson News Release 09/24/2015
A protein-coding gene called hnRNP K has been identified as a tumor suppressor for acute myeloid leukemia (AML), a finding that could be important for investigating how best to target treatment of a blood cancer striking mostly older individuals.
Expression of the protein-coding gene hnRNP K is significantly reduced in AML patients who carry a specific genetic deletion, according to a study led by .
Study results were published in the Sept. 24 issue of
¡°Our data implicates hnRNP K in the development of blood disorders and suggests it acts as a tumor suppressor,¡± said , assistant professor of . ¡°Both in vivo and in vitro results indicate that hnRNP K achieves this through regulation of key genetic pathways. Our study found that hnRNP K expression must be maintained for proper cellular regulation and to prevent tumor formation.¡±
Through use of a mouse model and cell lines, Post¡¯s team showed that reduced hnRNP K levels were associated with blood cancer. Their data revealed that AML patients who carried a partial deletion of chromosome 9 also experienced a significant decrease in hnRNP K expression. This deletion, 9q21.32, along with the decreased levels of hnRNP K, led to reduced survival and increased tumor formation.
HnRNP K was found to be haploinsufficient, in that it contained a single functional copy of a gene not capable of maintaining normal cellular function and leading to disease development.
¡°Our findings showed that hnRNP K haploinsufficiency led to tumor development by deregulating cell proliferation and differentiation programs through control of key cellular pathways, which suggests these pathways may be exploited by targeted therapies,¡± said Post. ¡°It was clear that these changes in AML patients with the 9q21.32 deletion resulted in a tumor suppressor gene involved in blood cancer development.¡±
MD Anderson study team members included Miguel Gallardo, Ph.D., Xiaorui Zhang, Ph.D., Aziz Nazha, M.D., Taghi Manshouri, Ph.D., Alfonso Quintas-Cardama, M.D., and Steven Kornblau, M.D., all of the Department of Leukemia; Hun Ju Lee, M.D., Department of Lymphoma & Myeloma; Carlos Bueso-Ramos, M.D., Ph.D., Department of Histopathology; Laura Pageon, D.V.M. and Mark McArthur, D.V.M., Department of Veterinary Medicine & Surgery; and Asha Multani, Ph.D. and Jan Parker-Thornburg, Ph.D., Department of Genetics. Also participating was Hospital Universitario, Madrid.
The study was funded by the National Cancer Institute (CA16672), the National Institutes of Health (P50 CA1000632-09); Leukemia Research Foundation, the Center for Genetics and Genomics Award, and Cancer Research Innovation Spain.