Navigation Links
Mouse model highlights histone methylation as distinguishing feature for leukemia subtypes
Date:11/3/2008

Research using a new mouse model has led to the identification of a potential therapeutic target for a type of leukemia commonly associated with an unfavorable prognosis. The study, published by Cell Press in the November issue of the journal Cancer Cell, also validates examination of histone modification as a strategy for distinguishing cancer subtypes.

MLL rearrangements have been observed in some cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). ALL patients with rearranged MLL have a relatively poor prognosis when compared with patients who have other types of ALL. Although several mouse models of MML-rearranged AML, modeling MLL-rearranges ALL has proven difficult. Recent studies have suggested that some MLL fusion proteins enhance gene expression by recruiting the histone H3 lysine79 (H3K79) methytransferase, DOT1L. Addition of a methyl group to histones plays an important regulatory role in the control of gene expression and is an example of an epigenetic change, a chemical alteration that does not change the DNA sequence.

"Aberrant recruitment of DOT1L to the promoters of MLL target genes may be a common feature of many oncogenic MLL fusion proteins. However, the extent of H3K79 methylation changes and the specificity of these epigenetic changes for MLL-rearranged leukemias have not been defined," says senior study author Dr. Scott A. Armstrong from the Dana-Farber Cancer Institute, Children's Hospital and Harvard Medical School.

Dr. Armstrong and colleagues created a mouse model in which conditional expression of MLL-AF4 induced both ALL and AML. They demonstrated that their model faithfully recapitulated human ALL resulting from MLL-AF4 translocation and identified a critical role for H3K79 methylation in MLL-AF4-driven gene expression and transformation. Importantly, suppression of DOT1L resulted in a reduction of methylated H3K79 and expression of critical MLL-AF4 target genes. "Our findings support the inhibition of DOT1L as a potential therapeutic approach in this disease and that this mouse model should be useful for assessment of therapeutic approaches for MLL-rearranged ALL," offers Dr. Armstrong.

"Our study also demonstrates that widespread differences in an epigenetic histone modification can distinguish different cancer subtypes and malignant versus normal cells," explains Dr. Armstrong. "Inasmuch as epigenetic modifications are likely to be linked to the maintenance of gene expression in many human malignancies, these strategies may be applicable to a wide variety of cancer subtypes."


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Mutant Mouse Gene Offers Clues to Hearing Loss
2. Mouse Study Finds Molecule That Tells Hair to Grow
3. Tumor suppressor genes speed up and slow down aging in engineered mouse
4. Mouse Skin Cells Reprogrammed to Act Like Embryonic Stem Cells
5. Mouse Adult Stem Cells Developed into Heart and Blood Cells
6. Mature Mouse Cells Reprogrammed to Stem Cell-Like State
7. Boston College biologists build a better mouse model for cancer research
8. Mouse model for mesothelioma reproduces human disease
9. Mouse study: Real-time imaging device may improve surgery for congenital colon disease
10. Seal Shield Introduces New Silver Seal Washable, Antimicrobial Mouse at HiMSS Healthcare Symposium
11. Mouse Model of Age-Related Macular Degeneration Developed
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due ... up a new, often overlooked aspect of head lice: the parasite’s ability to live away ... a common occurrence, but a necessary one in the event that lice have simply gotten ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... On Friday, ... presented a Bronze Wellness at Work award to iHire in recognition of their exemplary ... part of the 7th annual Maryland Workplace Health & Wellness Symposium at the BWI ...
(Date:6/24/2016)... ... 2016 , ... Marcy was in a crisis. Her son James, eight, was out of control. ... and physically. , “When something upset him, he couldn’t control his emotions,” remembers Marcy. ... rocks at my other children and say he was going to kill them. If ...
(Date:6/24/2016)... ... ... makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business for a Fair Minimum ... by 2020 and then adjusting it yearly to increase at the same rate as the ... wage floor does not erode again, and make future increases more predictable. , The company ...
(Date:6/24/2016)... Frederick, Maryland (PRWEB) , ... June 24, 2016 ... ... Mid-Atlantic Angels is actively feeding the Frederick area economy by obtaining investment capital ... support over the past 2½ years that have already resulted in more than ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016  In a startling report released today, ... residents by lacking a comprehensive, proven plan to eliminate prescription opioid ... ranking of how states are tackling the worst drug crisis in ... states – Kentucky , New Mexico ... . Of the 28 failing states, three – ...
(Date:6/23/2016)... 23, 2016 Capricor Therapeutics, ... a biotechnology company focused on the discovery, development ... patient enrollment in its ongoing randomized HOPE-Duchenne clinical ... 50% of its 24-patient target. Capricor expects the ... quarter of 2016, and to report top line ...
(Date:6/23/2016)... MOUNTAIN VIEW, Calif. , June 23, 2016 ... 9:00 a.m. CST on Thursday, July 7, 2016 , , ... kayla.belcher@frost.com ) , , , , EXPERT PANELISTS:  ... Sciences, Nitin Naik; Senior Industry Analyst, Christi Bird; Senior Industry Analyst, ... The global pharmaceutical industry is witnessing ...
Breaking Medicine Technology: