In a laboratory study, Upstate Medical University researcher Golam Mohi, Ph.D., his graduate student Yue Yang, and colleagues, have found that the loss of gene EZH2 promotes the development of Myelofibrosis (MF) in mice. The findings create a new pathway for study into the cause of MF and provide new therapeutic targets to block the progression of this rare form of blood cancer.
A paper on this study by Mohi's group was published recently in the medical journal Blood, the most cited peer-reviewed publication in the field of hematology, and highlighted in Blood Journal, a snapshot of the hottest studies from each week′s issue of Blood.
MF is a life-threatening progressive blood cancer in which bone marrow cells that produce blood cells become functionally abnormal due to deposition of fibrous tissues, leading to anemia and enlargement of the spleen and liver. There is no cure for MF, only treatments that help reduce symptoms of the disease.
"It is imperative to better understand the cause of the disease, so that more targeted therapies can be developed to help manage the disease, and optimally, to prevent the disease from progressing," said Mohi, associate professor of pharmacology in the College of Graduate Studies at Upstate.
Mohi's study stems from his previous investigations into the JAK2 mutation, known as JAK2V617F, which has been associated with three different Myeloproliferative Neoplasms (MPNs): Polycythemia Vera, Essential Thrombocythemia, and Myelofiborsis (MF).
Mohi says that works from his lab and other groups have established that JAK2V617F causes MPNs; however, it remained unclear as to how this single gene mutation could give rise to three different MPNs that have distinct clinical features. Mohi's study is focused on this issue.
"Current evidence suggests that although JAK2V617F is sufficient to induce one of the MPNs—Polycythemia Vera—additional mutations might be required to progress to MF," said Mohi. "A subset of patients with JAK2 mutant MF were found to have the loss of function mutations in EZH2. Using genetically engineered mouse models, we observed that concomitant deletion of EZH2 in mice expressing JAK2V617F reduces the red blood cells, increases the platelet counts and rapidly induces MF. This suggests that loss of EZH2 cooperates with JAK2V617F in the development of MF."
About 16,000 to 18,500 people in the United States have been diagnosed with MF. MF affects both men and women and can occur at any age, but people are usually over age 50 when they are diagnosed. Symptoms include bone pain, easy bleeding, bruising, fatigue, and weight loss.
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