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New insight into the cause of a rare blood cancer

With funding from Worldwide Cancer Research, Dr Golam Mohi and his colleagues have found that loss of activity of the EZH2 gene can allow the development of Myelofibrosis (MF) in mice. The findings reveal a new pathway which can now be studied to better understand the cause of MF and provide new therapeutic targets to block the progression of this rare form of blood cancer.

This work was recently published in the medical journal Blood, the most cited peer-reviewed publication in the field of hematology.

MF is a life-threatening, progressive blood cancer that affects both men and women.  It can occur at any age, but usually patients are over age 50 when they are diagnosed.  MF is characterized by abnormal scar tissue in the bone marrow which means the bone marrow cells can no longer produce red blood cells, leading to anaemia and enlargement of the spleen and liver. Other associated symptoms include tiredness, itching, bleeding and bone pain. There is no cure for MF, only treatments that help reduce symptoms of the disease and sadly, the overall survival for patients is less than 6 years.

“It is imperative to better understand the cause of the disease, so that more targeted therapies can be developed to help manage MF, and optimally, to prevent the disease from progressing,” said Dr Mohi, associate professor of pharmacology at Upstate Medical University in the USA.

Dr Mohi’s study stems from his previous investigations into the genetic mutation, known as JAK2V617F.  This mutation has been associated with three different blood conditions, collectively known as Myeloproliferative Neoplasms (MPNs) which can lead to MF. However, it remained unclear as to how this single gene mutation could give it was the focus of his current work.

“Previous evidence suggested that although JAK2V617F is sufficient to induce one of the MPNs, additional mutations might be required to progress to MF,” said r Mohi. “We found that a small group of MF patients with the JAK2 mutation were also found to have loss of activity mutations in EZH2. To prove there was a link, we used genetically engineered mouse models that have the JAK2V617F mutation and observed that loss of activity of EZH2 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.”

Dr Lara Bennett, Science Communication Manager at Worldwide Cancer Research said “Understanding MF at the molecular level is critical for the development of new therapies.  While this work is still very much in its early-stages, it is an important step forward for patients with this rare but devastating blood cancer.”

When asked about his support from Worldwide Cancer Research, Dr Mohi explained "Our ultimate goal is to find a cure for the deadly blood cancer MF. This research grant from Worldwide Cancer Research is extremely helpful in reaching that goal."

Press release written by Upstate Medical University press office and edited by Worldwide Cancer Research.