Can anyone explain hypermutated? That is suppo... - CLL Support
Can anyone explain hypermutated? That is supposedly my mutation testing result. All I have heard about is mutated or unmutated.
Dis you not ask your Onc to explain? Hypermutated means what is says. It a cancer that has mutated meaning it can be harder to treat.The non mutated forms are more responsive to the standard treatments.
Hi Wetumpka I think hypermutated is another way of describing mutated often used to describe IGHV mutational status
Grizzlebear I am afraid your information is not correct for CLL.
Mutational status in CLL normally refers to the status of IGHV, the late Professor Hamblin was a pioneer in discovering the significance of this. Hypermutated is a good prgnostic marker. In CLL unmutated IGHV is a poorer prognostic marker. it does sound counter intuitive CLL topics is a good place to learn about some prognostic markers and the significance of mutational status in CLL
Chaya Venkat CLL Topics 2011 "Prognostic Indicators: Who, When, What and Why" updates.clltopics.org/3695-...
Chaya venkat CLL Topics 2012 - “Doc, How Long Do I Have?” updates.clltopics.org/4336-...
Actually, mutated is a better prognostic factor than unmutated. I'm not much good on the I pad or I'd copy the link I just found on hypermutated CLL, but when I googled the term, I found a site that was an ASH educational guide. I hope you can find it. If not I'll get to it when I'm on my computer tomorrow.
Wetumpka, I think it is just another term for mutated, though I don't recall seeing the hypermutated term used before in CLL forums. When discussing prognostic testing for CLL, mutation has a specific meaning different that used when discussing the cause of cancers (i.e. mutated body cells that don't obey the instruction to die). B-Lymphocytes go through a process of sensitising to a particular foreign body or antigen which involves a hypermutation stage to come up with a vast number of protein rearrangements to find a specific lock/match to the antigen. They thereby mutate into a mature form that can generate antibodies against that antigen and eventually turn into plasma cells that can really churn out antibodies when the immune system is re-exposed to them.
A Testing Laboratory that provides this B-Lymphocyte mutation status test describes it thus:
"The immunoglobulin variable region heavy chain (IgVH) gene encodes antibodies that function in the immune response. IgVH mutation status identifies two CLL disease subtypes with differing clinical course: indolent and aggressive.
* Patients with hypermutated IgVH have a better prognosis
* Patients without hypermutated IgVH have a poorer prognosis
A sequence in the IgH gene that differs from its germline counterpart by >2% is defined as mutated.
~50-70% of patients with CLL have evidence of IgVH somatic mutations."
So it seems that you fall into the major category of CLL patients with a better prognosis, but by all means confirm that with your specialist.
Neil
Hypermutation is the fine tuning of the B cell receptor to a specific antigen. The very best cells go on to become plasma cells...
evolutionnews.org/2010/11/a...
IGHV@ is a family of genes and what matters perhaps as much as mutated or unmutated is which subtype is driving the CLL ... this is called Stereotypy.
For example patients with VH4-39 subtype 8 have 24 times greater chance of a Richter's transformation...
Here are some examples:
Stereotype #2 V3-21 mutated or unmutated, poor prognosis, antigentic stimulation by coffin-1, high frequency del 11q23.
Stereotype #8 V4-39, unmutated, surface IgG, poor prognosis, antigenic stimulation by vimentin, 17 fold risk of Richter's transformation, high frequency of trisomy 12.
Stereotype #4 V4-34, mutated, good prognosis, presentation at young age (~43), antigenic stimulation by Ii blood group.
Stereotype #16 V4-34, mutated, good prognosis - though not as good as #4.
Stereotype #1 V1-5-7, unmutated, poor prognosis, antigenic stimulation by vimentin.
Stereotype #5 V1-69, umutated, antigenic stimulation by coffin-1, favorable prognosis.
Stereotype #6 V1-69, unmutated, antigenic stimulation by non-muscle myosin heavy chain, prognosis intermediate.
It can be seen that family identity over-rides both the particular V gene used and the mutational status. There is obviously a lot more to come from this approach.
newevidence.com/oncology/en...
How complex?
bloodjournal.hematologylibr...
More from Dr. Hamblin
mutated-unmuated.blogspot.c...
More
