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Medical Forum / General / General / October 2005

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help understanding lymphoma

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O'Hush - 15 Oct 2005 14:59 GMT
Hi,

I'm hoping someone here can help me decipher some of the finer points of
Burkitt's diagnosis for a nursing school clinical assignment.  The points
I'm stuck on include:

I know what "FISH" is (fluoroescence in-situ hybridization) but not
"interface" FISH.  How would immunoglobulin heavy chains fuse, and if they
did, how would that be significant in Burkitt's?

The original phrase was:  (positive for) "IgH fusion" (by interface FISH)

Then there's this:  While I understand the definitions of all of the
following terms, I don't understand why it's important.

"High-intensity monoclonal surface IgG of lambda isotype."

Any help will be greatly appreciated.

Many thanks, --Patti
Robert - 15 Oct 2005 18:45 GMT
> Hi,
>
[quoted text clipped - 16 lines]
>
> Many thanks, --Patti

Cancer is the uncontrolled growth of a cell and all the other cells after it
are clones of the first. There is a lack of a normal variance.
B cells normally have immunoglobulin antibodies on their surface.
These are polyclonal cells originating from different mother cells and they
produce polyclonal antibodies on their surface.
The presence of monoclonal antibodies of either a single type such as lambda
or kappa is diagnostic of a monoclonal gammapathy resulting in light chain
disease. A good example of this is multiple myeloma.
In flow cytometry studies and FISH monoclonality denotes malignancy and
polyclonality is interpreted as benign.
O'Hush - 15 Oct 2005 20:21 GMT
> > Hi,
> >
[quoted text clipped - 20 lines]
> or kappa is diagnostic of a monoclonal gammapathy resulting in light chain
> disease.

Okay thanks -- that helps.

Regarding the "IgH fusion" question:  Did you address it above?  If so, I
didn't understand your answer.  The only article I found useful when I was
researching this issue before I asked the question mentioned "heavy chain
IgH fusion."  I haven't been able to find it again to see if I misread or
misunderstood it, and I haven't been able to find a source that explains
what IgH fusion is.  My wild guess before you posted this was that the heavy
chains of the antibody somehow fuse.  I was thinking maybe there's a
mutation that causes the protein chain to be mistranslated so the final
antibody is misshapen?  (I really have no idea.)

> A good example of this is multiple myeloma.
> In flow cytometry studies and FISH monoclonality denotes malignancy and
> polyclonality is interpreted as benign.

I was actually hoping to find out what "interface FISH" is as opposed to
plain old FISH.  But thanks -- that has given me a much better
understanding.

--Patti
Robert - 15 Oct 2005 23:59 GMT
> > > Hi,
> > >
[quoted text clipped - 46 lines]
>
> --Patti

I do not perform FISH so I would be only guessing here but it is a reagent
used in FISH in which Fluorescence in situ hybridization with immunoglobulin
heavy chain (IgH) is used. One Antibody is comprised of  light chains either
kappa or lambda and  heavy chains in which the entire antibody derives it's
name. An IgG contains gamma heavy chains and lambda or kappa light chains.
They all fuse to form an antibody (IgG).

The "interphase" relates to the stage in cell cycle division particularly
when the nuclear material is exposed. Other phases such as telephase
anaphase etc.........
You are doing a FISH when the cells are in interphase.

Again this is from my reading of it and corrections out there welcomed.
O'Hush - 16 Oct 2005 00:19 GMT
> > I was actually hoping to find out what "interface FISH" is as opposed to
> > plain old FISH.  But thanks -- that has given me a much better
> > understanding.
> >
> > --Patti

> I do not perform FISH so I would be only guessing here but it is a reagent
> used in FISH in which Fluorescence in situ hybridization with immunoglobulin
> heavy chain (IgH) is used. One Antibody is comprised of  light chains either
> kappa or lambda and  heavy chains in which the entire antibody derives it's
> name. An IgG contains gamma heavy chains and lambda or kappa light chains.
> They all fuse to form an antibody (IgG).

Sorry -- I still don't understand.  The entire sentence I'm having trouble
digesting is, "50% of nuclei positive for IgH fusion by interphase FISH."
Except of course "interphase" was spelled wrong, dammit (see below).  I
believe I more or less understand the normal structure of an antibody, but I
could certainly be mistaken.  If I understand correctly, that is what you
are describing above.  Why would the chart report a finding of normal
antibody structure?

> "interphase" relates to the stage in cell cycle division particularly
> when the nuclear material is exposed. Other phases such as telephase
> anaphase etc.........
> You are doing a FISH when the cells are in interphase.

Oh!  One mystery solved, anyway.  This looks like a transcription error.  I
have a printed copy of the admission history identical to the one signed by
the resident that says "interface FISH."

Thanks, --Patti
Robert - 16 Oct 2005 01:19 GMT
> > > I was actually hoping to find out what "interface FISH" is as opposed to
> > > plain old FISH.  But thanks -- that has given me a much better
[quoted text clipped - 19 lines]
> are describing above.  Why would the chart report a finding of normal
> antibody structure?

There is immunochemistry staining for kappa and lambda and then there is
cytogenetics and flow and FISH with the IgH and other BCL2 or c-MYC genes.
If the IgH is positive with BCL2 you have the IgH/BCL2 fusion.
You need to read up on it more that's all I can help you with.
Goodluck.

> > "interphase" relates to the stage in cell cycle division particularly
> > when the nuclear material is exposed. Other phases such as telephase
[quoted text clipped - 6 lines]
>
> Thanks, --Patti
O'Hush - 16 Oct 2005 15:25 GMT
> > > > I was actually hoping to find out what "interface FISH" is as opposed
> to
[quoted text clipped - 29 lines]
> You need to read up on it more that's all I can help you with.
> Goodluck.

Nope, I still don't get that part, but thanks for all your help.  You
definitely cleared up a few things for me.

--Patti
Bob - 16 Oct 2005 16:36 GMT
>> > Sorry -- I still don't understand.  The entire sentence I'm having
>trouble
[quoted text clipped - 17 lines]
>Nope, I still don't get that part, but thanks for all your help.  You
>definitely cleared up a few things for me.

I haven't followed the whole thread carefully, but if your question is
about the fusion... I suspect that the lymphoma is considered due to a
genetic fusion (translocation) between two genes, such as IgH and
BCL2. Finding the fused protein that results from the fused gene,
then, is diagnostic. I am not sure of the case you are discussing, but
I know that holds for some leukemias.

bob
O'Hush - 16 Oct 2005 19:22 GMT
> >> > Sorry -- I still don't understand.  The entire sentence I'm having
> >trouble
[quoted text clipped - 26 lines]
>
> bob

I know BLC2 and c-MYC are genes, but doesn't IgH refer to the heavy chain
portion of an immunoglobulin?  So are you saying that maybe the IgH is
mistranslated because of a fusion of BLC2 and c-MYC genes?

Unfortunately nearly everything I can find about this on the internet
assumes expertise I don't have.  I e-mailed my assignment this morning,
leaving out any mention of IgH fusion, so at this point it's just to satisfy
my curiosity.  I decided that my clinical instructor is unlikely to bring
out the chart and ensure that I've covered every point, and there's at least
a 50/50 chance that she doesn't understand this stuff either.  But it's
interesting.

Thanks, --Patti
Bob - 17 Oct 2005 04:33 GMT
>> >> > Sorry -- I still don't understand.  The entire sentence I'm having
>> >trouble
[quoted text clipped - 44 lines]
>
>Thanks, --Patti

Patti,

Go to PubMed and search on

IgH BCL2 fusion

You will get hits that deal with this explicitly. Just reading the
abstracts that come up will help you, I think.

I was guessing/inferring that the specific fusions of interest here
were between (the genes for) IgH and BCL2; that seems to be so. I
gather you are aware in general of gene fusions and their role in some
cancers.

bob
O'Hush - 17 Oct 2005 06:59 GMT
> >> >> > Sorry -- I still don't understand.  The entire sentence I'm having
> >> >trouble
[quoted text clipped - 60 lines]
>
> bob

Well, sort of.  Now.  : )  They're beginning to make *some* sense.  I
appreciate your help.

--Patti
 
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