Navigation Links
Common blood cancer may be initiated by single mutation in bone cells
Date:1/22/2014

NEW YORK, NY (January 21, 2014) Acute myeloid leukemia (AML) is a blood cancer, but for many patients the cancer may originate from an unusual source: a mutation in their bone cells.

In a study published today in the online edition of Nature, researchers at Columbia University Medical Center (CUMC) found that a mutation in the bone cells called osteoblasts, which build new bone, causes AML in mice. The mutation was found in nearly 40 percent of patients with AML or myelodysplastic syndrome (MDS), a precursor condition, who were examined as part of the study.

The researchers were able to stop production of leukemic blood cells in the mice with a drug that blocked the effects of the osteoblast mutation, suggesting that a similar drug may benefit a large portion of AML and MDS patients.

"If the mutation works the same way in humans, our study suggests practical ways that we may be able to intervene with a drug or an antibody. It may give us a tool for a disease that is rarely curable," said the study's lead investigator Stavroula Kousteni, PhD, associate professor of medical sciences in medicine and physiology & cellular biophysics at CUMC.

"This paper goes to the heart of bi-directional translational research, as it represents collaboration between institutions, as well as between clinicians and basic scientists," said Azra Raza, MD, director of CUMC's MDS Center and a co-author of the study. "The Kousteni Lab made the observation that a mutation affecting b-catenin in the bone marrow microenvironment cells of mice can cause leukemia. Clinicians from Memorial Sloan-Kettering and CUMC then extracted bone marrow samples of patients with MDS and AML from their tissue repositories, to confirm a similar pathway in a subset of patients. This incredibly important observation opens the possibilities of novel therapies for these dreaded diseases using non-chemotherapeutic approaches."

AML is one of the most common types of leukemia in adults, with about 15,000 cases diagnosed in the U.S. each year. The disease progresses rapidly, and only about 25 percent survive three years after diagnosis. MDS is a group of blood disorders diagnosed in about 10,000 people in the U.S. each year. Many people with MDS eventually develop AML.

Mutation of beta-catenin gene in osteoblasts causes AML in mice

In the current study, Dr. Kousteni and colleagues investigated a mouse strain that dies soon after birth from severe blood abnormalities. They found that the disease, which was the same as AML, was caused by a mutation in the beta-catenin gene in the animals' osteoblasts.

The mutation leads to cancer in adjacent bone-marrow stem cells through a series of events. First, the mutated beta-catenin protein moves from its normal location on the exterior of the osteoblast to the cell's nucleus, where it turns on production of a protein called jagged1.

Jagged1 proteins are then shipped to the osteoblast's exterior membrane, where they can bind to Notch proteinswhich activate signaling pathwayson neighboring bone-marrow stem cells. When this happens, Notch transmits signals inside the bone-marrow stem cells that ultimately transform the cells to leukemia.

When they looked at cells from AML and MDS patients, the researchers documented similar changes in beta-catenin, jagged1, and Notch signaling in 38 percent of the patients.

"Previous studies have shown that osteoblasts and leukemia blasts communicate with each other," said Ellin Berman, MD, a co-author of the study and leukemia clinician at Memorial Sloan-Kettering Cancer Center. "This study is the first to clarify exactly how that may happen."

New concept in cancer treatment

This study is the first to show that a mutation in one cell not only can influence nearby cancer cells but can cause cancer in another type of cell. Treating cancer by targeting nearby cells is a novel concept in cancer treatment, says Dr. Kousteni. "You're treating a cancer by targeting a cell that doesn't change instead of chasing the cancer cells, which constantly mutate and change.

"In AML, targeting jagged1 may stop the creation of new malignant cells; it would likely be used in combination with cytotoxic therapy. The first drug would prevent the emergence of new malignant cells; the second would eradicate the existing ones.

"The findings in this paper have crucial implications for our patients," said Siddhartha Mukherjee, MD, PhD, assistant professor of medicine at Columbia and a co-author of the study. "We have a growing armamentarium of drugs that target and kill cancer cells. But if cancer arises because of an interaction between a cell and its environment, we could potentially target that environment as well. Indeed, the cancer 'microenvironment' might be more amenable to drug therapy, as it likely has less of a propensity to mutate. At Columbia's MDS Center, we have been banking tissue samples of this cancer microenvironment, in addition to cancer cells. We hope to unleash all the resources now deployed on cancer cells to learn about, and target, cancer microenvironments,- the 'homes' that cancers grow in."


'/>"/>

Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert  

Related medicine news :

1. Chronic neck pain common among car crash victims, but most dont sue
2. “A Full List of Bad Habits,” a New Article on Vkool.com, Delivers To People 12 Common Bad Habits - V-kool
3. Winter Advisory: Ski Right - to Avoid Common Injuries!
4. KickinKitchen.TV to Partner with New York Common Pantry
5. Fatigue, a common side effect of breast cancer treatment, evaluated in novel patient study
6. Researchers discover common cell wall component in Chlamydia bacteria
7. Avoid Common Holiday Dangers with Safety Tips from ESA
8. From common colds to deadly lung diseases, 1 protein plays key role
9. REiNS collaboration seeks common outcome measures for neurofibromatosis clinical trials
10. Symple Surgical Inc. Completes Series A Common Stock Financing
11. American Society of Hematology releases list of commonly used tests and treatments to question as part of Choosing Wisely campaign
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Common blood cancer may be initiated by single mutation in bone cells
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Apple ... care services, staged a mock evacuation of the facility as part of a disaster ... Fire Department, Echo Hose EMS and Shelton City Emergency Manager, as well as the ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Global Healthcare Management’s ... Alexandria Park in Milford, NJ. This free event, sponsored by Global Healthcare Management’s ... The fun run is geared towards children of all ages; it is a ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the ... danger possible to save lost souls in the Philippines. “The Journey: From the Mountains ... a dedicated teacher of the Bible. She has taught all ages and currently teaches ...
(Date:10/12/2017)... ... October 12, 2017 , ... Planet Fitness, one of the largest and ... plans to open a flagship location in Covington, LA at 401 N. U.S. Highway ... store next to Office Depot in the Holiday Square shopping center. Its location allows ...
(Date:10/12/2017)... ... 2017 , ... Asante, a nationally recognized health system in ... existing home health joint venture through an agreement, effective October 1, 2017, to ... home health company with Asante, delivering clinically integrated care, for the past eight ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... -- NDS received FDA 510(k) clearance in May 2017 for its highly ... designed for endoscopy environments. An innovative secondary monitor solution, ZeroWire ... support the improvement of patient outcomes, procedural efficiency, and the lowering ... ... ...
(Date:10/4/2017)... 4, 2017  South Korean-based healthcare product Development Company ... "cprCUBE" on Kickstarter. The device will educate the user ... with better efficiency compared to the dated and pricey ... on efficacy of the compression for a more informed ... goal to raise $5,000. ...
(Date:10/2/2017)... 2017  Eli Lilly and Company (NYSE: ... third quarter of 2017 on Tuesday, October 24, 2017. ... day with the investment community and media to further ... call will begin at 9 a.m. Eastern time. Investors, ... webcast of the conference call through a link that ...
Breaking Medicine Technology: