The Fleischman Lab Continues Investigating the Role of Inflammation in MPN

2015 MPN Research Update

by Dr. Angela Fleischman

We are continuing to work on the role of inflammation in MPN.  The human immune system turns on the immune response when it recognizes invaders such as bacteria or viruses by producing inflammatory proteins, also called cytokines.  Cytokines are helpful to fight infection but if the immune response is not turned off after the infection is cleared this results in chronic inflammation.

Chronic inflammation is a feature of MPN

We have found that immune cells from MPN patients do not shut off production of inflammatory cytokines after stimulation.  This suggested to us that immune cells from MPN patients have a problem recognizing that they are supposed to turn off the immune response.

We find that MPN patient immune cells do not respond to regulatory signals that tell cells to turn off the immune response.  We are now identifying exactly where the problem is and determining whether JAK2V617F induces this abnormality in normal cells.  In addition, we are testing drugs for their ability to decrease the production of inflammatory proteins by MPN cells, candidate drugs that work well in the lab could then be developed into clinical trials for MPN.

Because chronic inflammation is a characteristic of MPN we are also investigating how this effects blood stem cells.  We are comparing the effect of chronic inflammation on normal versus JAK2V617F blood stem cells.  We predict that JAK2V617F will be more resistant to the negative effects of chronic inflammation on blood stem cells.  To do this, we are inducing chronic inflammation in MPN versus normal cells and determining how this effects their blood stem cell function.

Studying the Role of Lymphocytes in MPN development

We are also continuing to investigate the role of lymphocytes (another type of immune cell) in the development of MPN.  To do this, we are testing what happens in models of MPN when we remove certain types of lymphocytes.  We are also testing drugs that are known to target lymphocytes in laboratory models of MPN.

We are also working on developing a model for calreticulin (CALR) mutated MPN so this can be used to study how mutations in calreticulin lead to MPN.  There is little known about how mutations in calreticulin lead to MPN.  We are asking if the mutation makes the calreticulin protein move to abnormal locations in the cell.

My clinic at UC Irvine is now open and I am eager to see MPN patients.  We are also appreciative if any MPN patients in the Southern California area (or their relatives) are willing to donate blood for research.  Please contact me at agf@uci.edu if you are interested in a clinic visit or participation in donating blood.

I hope to open clinical trials at UC Irvine for MPN.  We currently have open a trial for atypical CML and CNL (closely related to MPN).  For more information on this trial, feel free to contact me.