Need Help Understanding New Gene Mutation in CLL/SLL

[PCara90]

Hello to everyone! Thanks to all for providing a safe, positive place to read about like souls sharing this same nasty journey. Every time I feel a cancer panic coming on, this is the first place I turn for comfort. I am a long time lurker but first time poster.

I was first diagnosed with CLL/SLL in 2015 and have been on watch and wait ever since with a semi-slowly, steadily climbing WBC count. 13q deleted and mutated, I thought I won the CLL lottery and hoped it would be long stretch to treatment, but the numbers are climbing and my lymph nodes are getting bulky and uncomfortable, so it looks like later is now turning into sooner.

My local hematologist, who I liked and trusted, left his practice (with only a postcard notification!) this past December. Since my WBC counts were approaching 100K anyway I decided it was time to visit a CLL specialist and flew out to MD Anderson for two days of tests, scans, pokes and prods. The results have been trickling in over the last couple of weeks and confirm the results found locally. 13q14 deletion; IGVH mutated. RBC and platelets are shrinking but only slightly lower than the bottom of the normal range. WBC 100K (98K Abs). Lots of visible swollen glands in my neck but no night sweats or weight loss and little to no impact on the spleen. I do get tired a bit more often now but it has never caused me to lose work days or interrupt my routine. I take care of myself and am a generally healthy 55 year old woman with no other health issues -- except this CLL beast!

Things were looking really good until tonight when the a scan of my "EndCLL Assay V1 Mutation Analysis Panel Results" from MD Anderson were posted. A mutation (or variant) of the BIRC3 gene was detected! All clear for ATM, BTK, NOTCH1, PLCG2, SF3B1 and TP53. I've never heard of this BIRC3 mutation so of course I've been reading everything I can find about it and it all sounds pretty bad! And very little is in layman terms, but the message is clear that this is an indicator of a more resistant mutation.

Anyone out there have any experience with the BIRC3 mutation? If so, are you on and one of the BTK inhibitors? Ibrutinib? I'm hoping this mutation responds well to the new therapies. I have an appointment with Dr. Alessandra Ferrajoli at MD Anderson on the 18th (who I know very little about, but she was very nice at our one meeting), but that leaves 17 more days of worrying!

[JR1964]

Well, in this crazy world of CLL we are as different as our own character. We may compare in some respect but differ in others. I do not know many of the fine details of the disease but can tell you there are many treatments out there as well as many more to come. As for MDA, I go there as a patient myself. My doctor is Dr. Weirda. Dr. Ferrajoli, Weirda, Jan, Keating and all the others are excellent in what they do. If it were not for Dr. Weirda I would be in treatment now. My previous Oncologist was not very informed as it comes to CLL. It is a great thing you are coming to MDA and a CLL SPECIALIST. STAY STRONG AND REMEMBER THAT A CURE IS COMING SOONER THAN LATER J.R.

[PCara90 in reply to JR1964]

Thanks J.R.! It helps tremendously to know their are others out there facing my same challenges. Your encouragement helps more than you can know!

I was highly impressed with MD Anderson - top to bottom. They run an impressive operation there. I remain hopeful about my disease and plan to go down fighting! I got a very good feeling about Dr. Ferrajoli even though we had little time together. I’ll be back in a couple of weeks so that we can plot my next move. More to come!

[JR1964 in reply to PCara90]

That's the spirit!! Do not let this crazy disease take over who you are. I was listening to one patient at MDA and had some of the worst markers. He was in treatment and doing great. I remember his words- " There are days I ask myself if I even have CLL" STAY STRONG J.R.

[annmcgowan]

Hi Cara my CLL specialist has told me not to worry too much about prognostics. Like JR says with CLL we are all very different. My fish test is all good but I am borderline for IGVH.

I am on Flair trial on Ibrutinib and rituximab arm and doing well. Apparently with the new drugs prognostics are not so helpful. Your fish test is still helpful when treatment decisions are being made as 17p del does not respond well to chemotherapy.

Many people on this site have reported early treatment with good prognostics and vice versus which for me supports my specialists advice.

My knowledge of prognostics is limited. I would like to learn more. However, I am following his advise and not worrying about them as new treatments come along.

I hope you find this reassuring.

Good luck and god bless.

Ann

[PCara90 in reply to annmcgowan]

Thanks Ann! Yes, I am quite positive and incredibly grateful for how far sciences has advanced in this area. It feels like we are so close to beating this thing! But there are still moments of panic , usually after I get a not-so-great test result (especially when I don’t completely understand it), when my mind jumps to worse case scenario. The folks here at this site always lift my spirits and bring the optimist in me back! Thanks for the encouragement and support!! It is truly appreciated!

[annmcgowan]

No problem Cara. I get like that too on occasion. I have a note to myself filed in notes on my I phone to remind me of the following:

1 That my current negative emotions are normal

2 That that all emotions are transient

3. That these too will pass.

It works for me.

Kind regards

Ann

[PCara90 in reply to annmcgowan]

Great reminders to keep on hand! I will add them to my notes as well. Yes, this too will pass!

[Hidden]

You should ask your doctors for more information on this. I might be wrong, I haven't read some of this stuff for almost a year but my recall is the BIR3 gene is associated with an 11q deletion and ATM deletion (I think you need the ATM deletion to get a BIR3 but that might be wrong). It also is related I think to the TP53 gene as well

This part I am not sure of either, but I thought it effected only CLL people treated with fludarabine?

I was unaware of it being a "less favorable marker" But again, you said you were 13Q deleted and I thought this was an 11Q thing. CllCanada can correct me if I am wrong....he is a walking encyclopedia of horror show facts.

Scott

[PCara90 in reply to Hidden]

Yeah, I’m having a hard time putting this all together. The report says TP53 and ATM were part of test and they were not singled out with mutations or variants. I am CD38 negative and ZAP70 negative as well. No 11q deletion or 17p or trisomy (per FISH and confirmed by BMB). And I’ve never been treated.

This new BIRC3 is the only thing that’s standing out. That and the 13q deletion. I am at intermediate stage with lots of swollen glands and 100k WBC, so this thing may be starting to morph but so far all these tests have left me more baffled than informed. I have a long list of questions for my upcoming appointment.

Thanks for your input! I’ll share what I find.

[AussieNeil Partner Administrator in reply to PCara90]

You quite likely have the highly desired IGHV mutated status being CD38 and ZAP-70 negative - about 70% probability. With respect to BIRC3, it's been mentioned in these previous posts: healthunlocked.com/search/b...

M D Anderson is the right place to find out what the likely outcome is for those sharing your prognostic factors and perhaps whether this may eventually help determine your best treatment options, but the path you take will be uniquely yours.

Neil

[PCara90 in reply to AussieNeil]

Yes, it has been determined that my CLL cells are mutated. I am very grateful for that! I have read everything I can find about this BIRC3 gene but it’s so very technical that I get lost before I can make any sense of things! It seems to be associated with an 11q deletion but that didn’t show up in my FISH or BMB.

I’m going to just try and relax for now and wait to see what my doctor at MDA has to say. Watch and worry - I’m sadly used to that!!

Thanks for the link! Maybe I can come back with some new information to share after my visit.

Pam

[PCara90]

So I thought I'd pop back in with an update about this BIRC3 gene mutation that popped up in my test results. I asked my doctor about it on Monday and she shrugged it off as nothing. No 11q deletions or other transformations as I had feared.

Apparently the extra test was looking for the other important somatic mutations of the TP53, ZAP-70 and NOTCH1 genes, all of which were negative for me (thank goodness).

So it appears I'll be starting treatment in about 2 months over at MD Anderson. I'll post back if this BIRC3 mutation comes up again, but for now I'm putting it out of my head and focusing on the positive news that my markers aren't so bad after all. More to come!