Metabolic Rewiring in Hairy Cell Leukemia

Here's a link to an interesting article on "BRAF-V600E Metabolic Rewiring and Reprogramming."

http://www.sciencedirect.com/science/article/pii/S1097276515004384

BRAF-V600E is the mutation present in nearly 100% of the classic form of hairy cell leukemia (and is also common in 50% of melanoma cases).

The metabolic cycle shown in the diagram may imply that a diet which promotes ketogenesis (such as a high protein, low-carb diet), may promote BRAF-V600E/MEK1 binding and tumor cell proliferation.

I'd be interested in understanding how levels of HMGCL compare between patients and whether there is a correlation to treatment success.

Interestingly enough, an HMGCL antibody has been produced in rabbits:
http://www.sigmaaldrich.com/catalog/product/sigma/hpa004727?lang=en&region=US

I wonder if such an antibody could be used to safely regulate HMGCL levels during treatment and reduce cell proliferation. 

A common mistake a lot of people initially diagnosed with HCL (including myself) make is to assume that HCL is like solid tumors and feeds on sugar.  They then follow a low carb diet, which in turn causes the body to invoke ketogenesis to metabolize fat and protein.  In so doing, they promote cell proliferation instead of starving the HCL. 

This is the mistake I made when being treated.  I wonder if it is one of the reasons why I did not respond as quickly as others to treatment during chemotherapy and my first round of Rituxan.  I stopped the diet before my second treatment of Rituxan and ultimately got a complete remission.

Just remember, "liquid cancers" aren't like solid tumors.  Follow a balanced diet, and let the medicine do its job.
 

Trial Announcement for Multiply Relapsed Hairy Cell Leukemia Patients

Multiply Relapsed HCL Patients:
If you're a multiply relapsed HCL patient looking for a non-chemotherapy treatment, consider the Moxe clinical trial at NIH.  This is a Phase 3 trial.

Results from the Phase 1 trial indicate there is no toxicity, a complete remission rate of 57%, and a majority of those patients were able to eliminate all signs of malignancy. These results are superior to many other non-chemotherapy treatments for relapsed HCL. Check out the webpage or call Dr. Kreitman at 301-648-7375.

Here's a great link for patients that explains the trial and how the drug works.

"Moxetumomab is a nonchemotherapy treatment that can produce MRD-negative complete remissions where patients have a chance to be free of disease for a long duration," he explained. "We have patients who have been free of MRD for more than 5 years now on moxetumomab, and more than 10 years on the parent drug, BL22."

Here's a link to the clinical trial protocol details.

This referral letter explains the trial to doctors looking for treatment options for their multiply relapsed and refractory HCL patients.
 

Hairy Cell Leukemia: Making an Impact...

About 2.5 years ago, I blogged regarding a new drug I read about and brought to the attention of the Hairy Cell Consortium.  It's a Bruton's Tyrosine Kinase (BTK) inhibitor known as PCI-32765, and was inspired by a rare disease known as XLA, in which the body doesn't produce B-cells due to a BTK gene defect.  Developed to treat NHL, when I read about it, I thought the underlying mechanism warranted investigation for treating HCL.

Here's a link to the post:

http://jonshclblog.blogspot.com/2010/11/i-want-new-drug.html

Well, the email describing the mechanisms and potential of the drug that I sent to the Hairy Cell Consortium had an impact.  They performed in vitro studies of the drug, and it was found to be highly effective in stopping HCL proliferation!

http://files.shareholder.com/downloads/PCYC/0x0x620800/0228F1DA-BFD9-4E43-9CD4-3688E1ECB36A/SAT_Poster_HCL-ASH2012_Sivina_FINAL_Dec_3_APPROVED.pdf

Clinical trials using this drug to treat relapsed and refractory Hairy Cell Leukemia patients are now underway at The Ohio State University Medical Center (Go Buckeyes!!!) and The Karmanos Cancer Institute in Detroit Michigan!

http://www.clinicaltrials.gov/ct2/show/NCT01841723?term=Hairy+Cell+Leukemia&rank=4

The drug goes by the trade name Ibrutinib.  Let's hope it lives up to the potential I anticipated in my post back in 2010!  Seems like our arsenal and options are really piling up.  Translational medicine and targeted therapies are taking off, and will hopefully make chemo a distant memory someday soon. 

On a personal note:    Back in April, I went on a 5 day trek to the Royal Arch Loop of the Grand Canyon South Rim with some friends from work.  It was awesome!  The second to last day we hiked 13 hours in 80 degree weather and ran out of water, so we banded a team of 5 together for a 3-hour night hike down to the Colorado River to collect 40 liters of water for the rest of the team (9 of us altogether), so we could hike out the next day.  Awesome!  5 years ago, I couldn't climb 13 steps without stopping to catch my breath.  The last day of the Royal Arch trek, I hiked 4000 feet vertically with 32 pounds on my back for over 7 miles and felt fantastic!!!

I go for my annual re-staging at NCI/NIH on June 26th.  Wish me luck...

Elves' Chasm

Rappelling down a canyon wall

The Ravine to Royal Arch Creek

The Royal Arch!

Desert Blossom

Toltec Beach on The Colorado River

Night Hike and Water Filtering Mission