Tag Archives: myeloproliferative neoplasms

Dr Vincelette on MYC Expression in Myelofibrosis

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Nicole D. Vincelette, PhD

Nicole D. Vincelette, PhD, postdoctoral fellow, Moffitt Cancer Center, discusses findings from a study investigating the role of MYC expression and S100A9-mediated inflammation in a subgroup of triple-negative myeloproliferative neoplasms (MPNs).

To determine how MYC expression drives MPNs, such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis, Vincelette and colleagues conducted a study in which they generated a mouse model that overexpresses MYC in the stem cell compartment. This analysis demonstrated that MYC overexpression was associated with the mice developing a myelofibrosis-like phenotype, which included anemia, atypical megakaryocytes, splenomegaly, bone marrow fibrosis, liver fibrosis, spleen fibrosis. The mice also experienced adverse clinical outcomes, such as reduced overall survival (OS), compared with wild-type mice, Vincelette says.

Since the MYC-overexpressed mice developed myelofibrosis, the next step of this research was to investigate how MYC drives myelofibrosis, Vincelette explains. Investigators performed single-cell RNA sequencing to compare the bone marrow cells from MYC-overexpressed and wild-type mice. MYC overexpression correlated with upregulation of the S100A9 protein, which contributes to inflammation and innate immunity, according to Vincelette. Therefore, MYC drives the development of myelofibrosis through S100A9-mediated chronic inflammation. To validate the role of S100A9 downstream of MYC in myelofibrosis, investigators created a mouse model with S100A9 knockout in the presence of MYC overexpression, Vincelette notes. The S100A9 knockout protected against the development of myelofibrosis phenotype in that mouse model, Vincelette emphasizes.

By generating a mouse model that overexpresses S100A9, investigators also determined that S100A9 overexpression alone contributes to the development of myelofibrosis phenotypes, Vincelette says. When investigators treated the MYC-overexpressing mice with the S100A9 inhibitor tasquinimod (ABR-215050), the agent only partially abrogated the myelofibrosis phenotype, meaning the mice had reduced atypical megakaryocytes and splenomegaly. Additionally, the mice developed anemia and no OS difference occurred between tasquinimod and vehicle treatment, potentially because of off-target drug effects, Vincelette concludes.

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Three Key Relationships Bring New Drugs to the MPN Community

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 Byline:  Ann Brazeau, CEO & Founder

MPN Advocacy and Education International prides itself on bringing the experts to the MPN Community to ensure they are receiving accurate and updated information about clinical trials, treatment options, quality of life issues, and everything that could affect them medically.  It also brings biopharmaceutical companies together with the researchers/clinicians at all of their programs in an effort to inform both physician and patient who is doing what in the laboratories around the world that could bring a new drug to commercialization for their use.

These three relationships are critical to new drug development.  Our Industry Partners’ research and development teams work tirelessly in their labs to find answers to perplexing questions myeloproliferative neoplasms present.  The MPN specialists who give so much of their time to speak at our programs, spend hours in their labs and also see patients throughout each day to understand the complexities of MPNs and how to best treat each patient, and many participate in heading trials at their academic and medical institutions.  Patients participate and commit to lengthy clinical trials to help discover what works and what doesn’t.  Without them, drugs would not be developed or approved. Drugs have to be tested for safety and efficacy in patients.  There is no way around this fact.  Hats off to those who volunteer to participate in clinical trials in hopes that the drug may one day benefit others who have the same condition as theirs.  Participation in a clinical trial is a major contribution to our society.

Learn more about MPN clinical trials

This intricate connection is the key to so many discoveries that have saved lives, cured the common headache, stopped seizures, and cured some cancers.  While preclinical research answers basic questions about a drug’s safety, it is not a substitute for studies of ways the drug will interact with the human body.  People living with a chronic disease, like an MPN, benefit enormously from the pipeline of medications brought to market by hard-working clinical researchers who design and carry out clinical trials that show promise after testing in animals.

Education is critical to the success of clinical trials and participation.  If physicians that treat you are not aware of the numerous trials currently underway, is it your responsibility to share what you know? We would say yes.  Our programs for physicians that treat MPN patients always includes updates about current trials to be sure they are made aware of every single trial in the MPN space.  This information coupled with site locations and trial criteria are essential to connecting the patient to a specific trial.

In this era of individualized treatment protocols and combination therapies, which will eventually be widespread in not only MPNs but other disease areas, it would be a shame to miss opportunities where potentially good therapies might fall off the grid for lack of trial participants and trial sites due to already strained programs.  With the robust activity in MPNs currently, the challenges accompany the gains.  Thus, the relationships among the three groups is even more important.

MPN Advocacy and Education International understands the challenges experienced by all three entities.  Each plays an integral role in bringing new drugs to the shelves and ultimately to patients.  Researchers who participate in trials and see patients can be overwhelmed.  Patients may have financial issues that prohibit a commitment to a trial even if they want to participate.  There are social and cultural factors that have historically left many trials with one demographic of participants, namely white, insured, and often retired.

The good news is organizations and our partners want to understand the challenges and want to help in all ways.  In the seventeen years I’ve been working in MPNs, I am seeing the fruits of our advocating and educational efforts not only for patients, but in our relationships with biopharmaceutical companies and the hundreds of physicians who are not necessarily MPN specialists that see MPN patients.  Our engagement and desire to grow a deeper understanding of the many challenges patients face has created a real interest in finding ways to close the gaps in areas of access, participation, education, and support.

Without collaboration and communication, the momentum needed for new drug development would quickly lose steam.  MPN Advocacy and Education International remains committed to providing a platform for the dialogue necessary to keep the wheels in motion.

View our MPN Clinical Trials 101 Webinar

 

 

MPN Specialists Videos

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MPN Advocacy & Education International partnered with MPN specialists to offer insights on patient concerns and updates on drug treatments during this pandemic. The videos are now available on our YouTube channel, click here to subscribe.

These videos are made possible by a grant from Bristol Myers Squibb

Naveen Pemmaraju, MD-MD Anderson Cancer Center

 

Mark Heaney, MD, PhD-Columbia University Medical Center

 

Ellen Ritchie, MD-Weill Cornell Medicine

 Linda Smith-Resar, MD-Johns Hopkins

Dr. Resar’s presentation will be posted as soon as it is available.

One Patient’s Point of View on “Living” with Myelofibrosis

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David told his story at the Cleveland MPN Patient Program in November

On a beautiful fall day in late August 2013, I received a call that changed the course of my life. The voice on the other end told me that they had reviewed my blood counts and determined that I had some sort of leukemia. They had pre-admitted me to the local hospital to meet an oncologist and have the necessary tests. After about two weeks I received my diagnosis of Primary Myelofibrosis, Intermediate 1. I was told that treatment options were limited and the only true cure was allogeneic bone marrow transplan

It is tempting to focus all our energies on our hope in medical interventions. But diagnosis brings fear, denial, anger, & depression. These impact your relationships and can throw you into a downward spiral. Being diagnosed with a life-threatening disease like an MPN is an existential challenge. It raises all the questions: Why are we here? What is life about? What lies beyond this life? How you answer these questions will affect how you deal with your disease and its physical effects.

We are all tempted to be sad and maybe even angry. But you do not have to give in to the negative. You can choose to respond with a positive attitude.

 

My diagnosis has changed the course of my life – but for the better. Because of myelofibrosis, I realized that I was spending far too much of my time and energy focused on some sort of future achievement. I was super-busy every day and the days passed in a blur. But myelofibrosis woke me up to the truth that life is not about some future achievement. Life is about today. Since my diagnosis, I have come to have a heightened enjoyment of the simple pleasures of daily living.

These last six years have been wonderful and I have enjoyed them more because of my disease. My son and his wife have been kind enough to give us two new grandchildren in the past four years – and I am making the most of that. I’ve made many good friends in the MPN community.  I took up motorcycle riding.  The more aware I am of my mortality – the more I savor every experience of life.

Your life only comes one day at a time. Today is the day you have – make it into something good. Refuse to let an uncertain future rob you of today’s joys.

David shared his story in the MPN Community Connection Newsletter click here to view

 

David is the support group coordinator for the northern Pennsylvania/Ohio area, if you are interested in participating you can contact us for more information. Click here to contact us.