All Hail Ra

I know it's been too long since my last post!

I've got lots to discuss and I'm short on time right now, but I wanted to share an interesting "Science Daily" article that I just found.

http://www.sciencedaily.com/releases/2011/06/110608195159.htm

It states:

The researchers demonstrated that B-cells are deficient in one of the main DNA repair pathways, known as Nucleotide Excision Repair. This pathway repairs a lot of different DNA lesions, including UV-induced damage and chemical adducts (e.g. from air pollution and cigarette smoke). Their model therefore explains why strong UV exposure (e.g. unprotected sun bathing) is the number one environmental risk factor for lymphoma and also supports the evidence that exposure to air pollution and smoking are also risk factors.

Dr Nouspikel said: "Lymphoma is one of the ten most frequent cancers in adults in the UK, and the third among children. If we want to come up with efficient strategies for prevention and therapy, it is crucial to understand what causes it. The novel mechanism we have discovered potentially accounts for the development of many different types of lymphoma. It may also explain why strong exposure to sunlight is the main environmental risk factor for this cancer."

This supports my theory than sunlight may cause mutations (specifically cytosine deamination to uracil in RNA) that cause HCL!  Likewise, it reinforces my hypothesis that the reason they can't sequence my hairy cell DNA is because there is a mutation in my DNA corresponding to the primer they're using which the DNA repair enzymes either failed or don't attempt to repair.
I've got lots more to talk about, like mcl-1 inhibitors and new data at 15 weeks after my last Rituxan treatment that supports my Rituxan-related late onset neutropenia (LON) hypothesis, but it'll have to wait until I have more time.  I'm still waiting to get my latest flow results.

There was a huge Coronal Mass Ejection (CME) 2 days ago that spanned half the surface of the sun and is headed our way, so wear sunscreen!

Later.
6/11/2011 update

Wow!  Just one day later, one of my fellow HCL'ers (shout out to Vincent) found this announcement:

http://www.medpagetoday.com/HematologyOncology/Leukemia/27009

It states that HCL has been narrowed down to a single common gene mutation, BRAF V600E.  BRAF is a gene most widely known for its involvement in melanoma.  This is groundbreaking, and since the leading cause of BRAF V600 mutation is excessive sun exposure, gives further credence to my hypothesis that sun exposure is a leading cause of HCL.  All these studies are starting to add up and reinforce that hypothesis.  It also means that clinical trials with BRAF V600E inhibitors like PLX-4720, which are highly active in treating melanoma, are warranted in patients with refractory and relapsed HCL.  Perhaps a PLX4720-assisted Cladribine / GA-101 trial in refractory and relapsed HCL'ers is in the future...

Here's the published study.

These findings may lead to the development of mouse models for HCL research: 

"On the basis of our findings, it should be feasible to develop murine models of HCL by activating the RAS–RAF–MAPK signaling pathway in specific B-cell subpopulation."

"Strikingly, a T→A transversion occurring at position 1860 of the messenger RNA RefSeq NM_004333.4 and resulting in the V600E variant was found in samples from all 47 patients with HCL..."

I'm hypothesizing that the transversion is sunlight induced.  It will be interesting to see if research related to the first study I cited can determine whether DNA excision repair related to BRAF V600 is inactive during certain stages of B-cell maturation (specifically en route or at the germinal center stage).

It's all coming together.  Needless to say Eddie Vedder's "Hard Sun" is going to be the backup soundtrack for my next bloodcount video...