Hello all,
I am trying to understand the significance of Chromosomal Abnormalities upon conventional cytogenetics and FISH.
I am trying to clarify my layman's understanding.
3 categories:
Hypodiploid (deletions and/or gains)
Hyperdiploid (trisomes/extra copies); and
IgH translocations, each translocation is risk stratified accordingly - high, intermediate, standard.
Hypodiploid is High Risk. associated with a poorer prognosis and prone to clone variance.
Hyperdiploid is Standard Risk and is the "best" to have with the most favorable outcome and tends to remain stable/constant throughout your disease, with little to no risk of clone variance.
Some IgH translocations are "better" than others, best one to have is t (11:14), standard risk, which is more favorable to treat initially and usually results in longer remission;, but becomes more difficult to treat upon relapse. (If this is accurate, why is that the case?)
In addition to trying to clarify my understanding I would like to know the following based upon the above: if you have the standard risk t (11:14) translocation, does the risk and abnormality remain stable or constant throughout the course of the disease (similar to what happens if you are hyperdiploid) or is there a risk - prone to clone variance somewhere along the disease course (similar to what happens if you are hypodiploid).
I hope I am making some kind of sense. Thanks to all who try to help.
All the very best,
Forums
7 posts
• Page 1 of 1
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Need Help w/ Understanding Chromosomal Abnormalities
Hello everyone
Is there anyone that might be able to clarify what I hope to understand ? Thanks in advance ! All the best,
Dana
Is there anyone that might be able to clarify what I hope to understand ? Thanks in advance ! All the best,
Dana
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DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Need Help w/ Understanding Chromosomal Abnormalities
The Mayo Clinic guidelines mentioned in this thread,
https://myelomabeacon.org/forum/mayo-clinic-multiple-myeloma-guidelines-2013-t1810.html
have a stratification of myeloma patients into three risk categories -- standard, intermediate, and high risk. The guidelines also describe the criteria (chromosomal abnormalities) Mayo uses to determine which category a myeloma patient falls into.
There is not, as far as I know, any widely accepted consensus statement on what defines a patient's risk classification. The Mayo guidelines are the opinions of the Mayo specialists, but they are not necessarily the final word on the subject.
https://myelomabeacon.org/forum/mayo-clinic-multiple-myeloma-guidelines-2013-t1810.html
have a stratification of myeloma patients into three risk categories -- standard, intermediate, and high risk. The guidelines also describe the criteria (chromosomal abnormalities) Mayo uses to determine which category a myeloma patient falls into.
There is not, as far as I know, any widely accepted consensus statement on what defines a patient's risk classification. The Mayo guidelines are the opinions of the Mayo specialists, but they are not necessarily the final word on the subject.
Re: Need Help w/ Understanding Chromosomal Abnormalities
Dana H wrote:
> 3 categories:
> Hypodiploid (deletions and/or gains)
> Hyperdiploid (trisomes/extra copies); and
Hi Dana.
It's actually slightly more complicated. A normal cell's DNA has 23 pairs of chromosomes. If you have fewer than 46 total, it's hypodiploid (fewer than 2 of at least some chromosome), and if you have more than 46 it's hyperdiploid (perhaps 3 of a chromosome, which is a trisome). These are cases of an entire chromosome being missing or extra. In addition, it's possible for just part of a chromosome (one gene or part of a gene) to be missing; that's a deletion. In multiple myeloma, the most troublesome one of these is del(17p13.1), which means that some material on the short (p for petite) arm of chromosome 17 at position 13.1 is missing,
> IgH translocations, each translocation is risk stratified accordingly -
This means that a particular DNA sequence is appearing on the wrong gene or chromosome.
> Hypodiploid is High Risk. associated with a poorer prognosis and prone to
> clone variance.
>
> Hyperdiploid is Standard Risk and is the "best" to have with the
> most favorable outcome and tends to remain stable/constant throughout your
> disease, with little to no risk of clone variance.
My simple understanding is that extra doesn't hurt, but when something is missing it's a problem. However, I have never heard of your finding that hypodiploidy is stable while hoperdipoidy is not. Can you cite a reference for this?
> Some IgH translocations are "better" than others, best one to
> have is t (11:14), standard risk, which is more favorable to treat
> initially and usually results in longer remission;, but becomes more
> difficult to treat upon relapse. (If this is accurate, why is that the
> case?)
I'm not so sure that any chromosomal abnormality is good. But among those that are commonly found in multiple myeloma, certain ones are associated with poor prognosis. As far as I know, these are merely statistical correlations of outcomes with cytogenetics for many patients. For the most part, the cause-and-effect relationship between the abnormalities and disease progression is unknown.
> In addition to trying to clarify my understanding I would like to know the
> following based upon the above: if you have the standard risk t (11:14)
> translocation, does the risk and abnormality remain stable or constant
> throughout the course of the disease (similar to what happens if you are
> hyperdiploid) or is there a risk - prone to clone variance somewhere along
> the disease course (similar to what happens if you are hypodiploid).
The usual course of multiple myeloma is that the cancerous plasma cells develop additional mutations, and this is the main reason that the disease is still considered incurable. If the therapy is not able to destroy all of the cancerous cells, those that survive eventually mutate so as to become resistant to the therapy. Switching to a different drug often helps, but only for a while. I have not seen any studies which look specifically at the high-risk abnormalities that have now been identified to see whether they can be absent at diagnosis but develop later, and if so how often that happens.
My impression is that there is a lot about this disease that nobody understands yet. The good news is that a lot of smart people are working very hard to figure it out.
I hope this is of some help.
Best wishes,
Larry D'Addario
Pasadena, CA
[I have no medical training, but I've read a lot of the medical literature on multiple myeloma since my wife was diagnosed in Sep 2012. I'm especially interested in the genetic abnormalities because she has two of the worst ones, del(17p) and t(4;14).]
> 3 categories:
> Hypodiploid (deletions and/or gains)
> Hyperdiploid (trisomes/extra copies); and
Hi Dana.
It's actually slightly more complicated. A normal cell's DNA has 23 pairs of chromosomes. If you have fewer than 46 total, it's hypodiploid (fewer than 2 of at least some chromosome), and if you have more than 46 it's hyperdiploid (perhaps 3 of a chromosome, which is a trisome). These are cases of an entire chromosome being missing or extra. In addition, it's possible for just part of a chromosome (one gene or part of a gene) to be missing; that's a deletion. In multiple myeloma, the most troublesome one of these is del(17p13.1), which means that some material on the short (p for petite) arm of chromosome 17 at position 13.1 is missing,
> IgH translocations, each translocation is risk stratified accordingly -
This means that a particular DNA sequence is appearing on the wrong gene or chromosome.
> Hypodiploid is High Risk. associated with a poorer prognosis and prone to
> clone variance.
>
> Hyperdiploid is Standard Risk and is the "best" to have with the
> most favorable outcome and tends to remain stable/constant throughout your
> disease, with little to no risk of clone variance.
My simple understanding is that extra doesn't hurt, but when something is missing it's a problem. However, I have never heard of your finding that hypodiploidy is stable while hoperdipoidy is not. Can you cite a reference for this?
> Some IgH translocations are "better" than others, best one to
> have is t (11:14), standard risk, which is more favorable to treat
> initially and usually results in longer remission;, but becomes more
> difficult to treat upon relapse. (If this is accurate, why is that the
> case?)
I'm not so sure that any chromosomal abnormality is good. But among those that are commonly found in multiple myeloma, certain ones are associated with poor prognosis. As far as I know, these are merely statistical correlations of outcomes with cytogenetics for many patients. For the most part, the cause-and-effect relationship between the abnormalities and disease progression is unknown.
> In addition to trying to clarify my understanding I would like to know the
> following based upon the above: if you have the standard risk t (11:14)
> translocation, does the risk and abnormality remain stable or constant
> throughout the course of the disease (similar to what happens if you are
> hyperdiploid) or is there a risk - prone to clone variance somewhere along
> the disease course (similar to what happens if you are hypodiploid).
The usual course of multiple myeloma is that the cancerous plasma cells develop additional mutations, and this is the main reason that the disease is still considered incurable. If the therapy is not able to destroy all of the cancerous cells, those that survive eventually mutate so as to become resistant to the therapy. Switching to a different drug often helps, but only for a while. I have not seen any studies which look specifically at the high-risk abnormalities that have now been identified to see whether they can be absent at diagnosis but develop later, and if so how often that happens.
My impression is that there is a lot about this disease that nobody understands yet. The good news is that a lot of smart people are working very hard to figure it out.
I hope this is of some help.
Best wishes,
Larry D'Addario
Pasadena, CA
[I have no medical training, but I've read a lot of the medical literature on multiple myeloma since my wife was diagnosed in Sep 2012. I'm especially interested in the genetic abnormalities because she has two of the worst ones, del(17p) and t(4;14).]
-
LarryD - Name: Larry D'Addario
- Who do you know with myeloma?: wife
- When were you/they diagnosed?: September 2012
- Age at diagnosis: 65
Re: Need Help w/ Understanding Chromosomal Abnormalities
Hey Terry H and Larry ,
Thank you so much for taking the time to help me understand. It is much appreciated.
@ Larry,
>However, I have never heard of your finding that hypodiploidy is stable while hoperdipoidy is not. Can you cite a reference for this?
I will have to see what I can find to cite my layman's understanding of what I wrote:
> Hyperdiploid is Standard Risk and is the "best" to have with the
> most favorable outcome and tends to remain stable/constant throughout your
> disease, with little to no risk of clone variance.
I will check my "notes" and see what I can come up with in support of what I wrote, but with that said, I also know I could be so totally totally wrong as I struggle with understanding a great deal about this disease spectrum and look to the members on this forum for correction and clarification.
All of the very best to you both.
Dana H.
Thank you so much for taking the time to help me understand. It is much appreciated.
@ Larry,
>However, I have never heard of your finding that hypodiploidy is stable while hoperdipoidy is not. Can you cite a reference for this?
I will have to see what I can find to cite my layman's understanding of what I wrote:
> Hyperdiploid is Standard Risk and is the "best" to have with the
> most favorable outcome and tends to remain stable/constant throughout your
> disease, with little to no risk of clone variance.
I will check my "notes" and see what I can come up with in support of what I wrote, but with that said, I also know I could be so totally totally wrong as I struggle with understanding a great deal about this disease spectrum and look to the members on this forum for correction and clarification.
All of the very best to you both.
Dana H.
-
DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Need Help w/ Understanding Chromosomal Abnormalities
Good Morning Larry,
I located my source, the article which gave me the understanding of Hyperdiploid "stability". Again, I was trying to clarify if my simplified statement /understanding was accurate with my posted question, trying to see if I was headed on the "right" track. Thanks again for your help.
Best, Dana
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659977/#!po=95.8333
http://www.ncbi.nlm.nih.gov/pubmed/22498740
I located my source, the article which gave me the understanding of Hyperdiploid "stability". Again, I was trying to clarify if my simplified statement /understanding was accurate with my posted question, trying to see if I was headed on the "right" track. Thanks again for your help.
Best, Dana
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659977/#!po=95.8333
http://www.ncbi.nlm.nih.gov/pubmed/22498740
-
DanaH - Who do you know with myeloma?: Myself, SMM as of 1/2012
- When were you/they diagnosed?: 1/2012
- Age at diagnosis: 54
Re: Need Help w/ Understanding Chromosomal Abnormalities
@LarryD - You wrote "A normal cell's DNA has 23 pairs of chromosomes. If you have fewer than 46 total, it's hypodiploid (fewer than 2 of at least some chromosome) ..."
It's a minor point, but since we're going into this in-depth, I think the definition of hypodiploidy when it comes to humans (who usually have 23 pairs of chromosomes) is a bit more subtle than just "less than 46 chromosomes".
Whenever I've seen the definition actually spelled out, hypodiploidy is defined as having 44 or less chromosomes.
This means that, in those odd cases where someone might have one fewer chromosome than the standard 46, they are not actually defined as being hypodiploid, but as something else called "pseudodiploid".
See, for example, the definition in this paper,
http://www.haematologica.org/content/early/2013/05/03/haematol.2012.081083.full.pdf
which is as follows: "hyperdiploid multiple myeloma (≥47 and <75 chromosomes; H-MM) and non-hyperdiploid multiple myeloma (NH-MM) (1). NH-MM is further divided into 3 subgroups: Hypodiploid (≤44 chromosomes), pseudodiploid (45-46 chromosomes) and near tetraploid (>75 chromosomes) ..."
It's a minor point, but since we're going into this in-depth, I think the definition of hypodiploidy when it comes to humans (who usually have 23 pairs of chromosomes) is a bit more subtle than just "less than 46 chromosomes".
Whenever I've seen the definition actually spelled out, hypodiploidy is defined as having 44 or less chromosomes.
This means that, in those odd cases where someone might have one fewer chromosome than the standard 46, they are not actually defined as being hypodiploid, but as something else called "pseudodiploid".
See, for example, the definition in this paper,
http://www.haematologica.org/content/early/2013/05/03/haematol.2012.081083.full.pdf
which is as follows: "hyperdiploid multiple myeloma (≥47 and <75 chromosomes; H-MM) and non-hyperdiploid multiple myeloma (NH-MM) (1). NH-MM is further divided into 3 subgroups: Hypodiploid (≤44 chromosomes), pseudodiploid (45-46 chromosomes) and near tetraploid (>75 chromosomes) ..."
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