Tag Archives: myelofibrosis

Dr Vincelette on MYC Expression in Myelofibrosis

Posted on by

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.

Read more

MPN Specialists Videos

Posted on by

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

Posted on by

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.

 

 

 

 

Caregiving: What I’ve Learned

Posted on by

By Stephen W.

My wife was diagnosed with ET (Essential Thrombocythemia) in 2007. Since then, her health issues have varied. For several months, she will do very well with little to no problems, and then an episode that has included an ER visit on occasion, will throw us into action mode. Even our children know what is expected of them. We all becoming a caregiving team.

Caregiving has many layers. It requires endurance, listening skills, humility, open mindedness, flexibility, wisdom, empathy, managerial skills, problem solving skills, healthy choices, rest, outlets, support and in many ways, the needs similar to those we care for, except that we have to be willing to be the strength BEHIND the patient.

Endurance. There will be days when the one you are caring for requires everything you’ve got. It is easy to get burnt out. You may find yourself doing it all and feeling a bit resentful, at times. My suggestion is to get a backup caregiver. So many people offer help and we graciously decline with a thank you and assurance that we are okay. I now say, thank you and how can you help? Getting help doesn’t mean you are shrugging your responsibilities or care less about your loved one. It is a wise decision when times are tough. Sometimes just having someone grocery shop is a great gift.

Humility. Caregiving is not about you. I’ve learned to keep my place and learn from my wife and those that administer her medical care. I don’t have all the answers. My role is vital but there is no room for an ego.

Managerial skills. I never dreamed the managerial skills I learned in my career would come in handy for caregiving. Managing appointments, medical needs, insurance companies, children, household needs, and day to day care for the patient can be overwhelming without a system. When times are tough we run a tight ship with each of us knowing our role and responsibilities. Delegating is a way of life. We’ve learned to adjust quickly and as needed.

Keeping EVERYONE healthy. Parenting and caregiving for an adult are very similar. If we aren’t healthy, everyone suffers. Proper nutrition, exercise, rest, and finding outlets and support are essential. Recognize when you need a break and take it.

The Rewards. I’ve never felt closer to my wife. Our family is stronger and we know we can rely on one another. I’ve learned a lot about ET, but equally about life and love.

Click here for more Caregiver Resources