Has anyone heard about the Maf gene in myeloma.? I am specifically interested in the prognostic value of a missing Maf gene. I have of course googled it but unable to find something I can understand.
Kind regards
Michelle
Forums
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Re: Maf gene
Hi Meesh,
Yes, I have heard of it.
Be on the lookout for MEK inhibitor therapy!
To date GEP identifies 7 types of multiple myeloma..MAF being one of them.
MAF is also identified as t14:16 (c-MAF), t(14,20) (MAF-B) and 8q24.3 (MAF-A)
MAF is found in 5-7% of all newly dx multiple myeloma cases and is associated with more aggressive multiple myeloma and shorter survival. Patients with MAF have significantly inferior survival when treated with hi-dose chemo and auto BSCT.
MAF is an oncogene that stimulates proliferation of multiple myeloma plus it increases interactions between multiple myeloma cells and stromal cells. It enhances proliferation and adhesion to bone marrow through activation of CCDN2 and integrin 7 genes. MAF genes are important to the malignant potential of multiple myeloma. MAF induces ARK-5 elevation. ARK-5 induces tumor invasion via IGF-1 elevation of AKt.
I do understand how all those alphabet descriptors can get quite confusing.
Avet Loiseau in Blood 2010 did challenge the negative prognosis and stated there was no difference in overall survival with t(14:16) based on a retrospective analyses of ~1K patients.
http://bloodjournal.hematologylibrary.org/content/117/6/2009.abstract
Recently Popovic noted (Feb 2011Blood) Annuziata et al (April 2010Blood) who identified a group of agents called MEK inhibitors as being effective vs. MAF.
http://bloodjournal.hematologylibrary.org/content/117/8/2396.abstract?ijkey=bcaa36f17c3606f3db0734cf148492b78434c690&keytype2=tf_ipsecsha
http://bloodjournal.hematologylibrary.org/content/117/8/2300.full
Did your FISH report identify a MAF translocation? Mine did.
So far, based on ASH2011 there seems to have been moderate success with the MEK inhibitor, selumetinib, in refractory multiple myeloma patients
http://ash.confex.com/ash/2011/webprogram/Paper42295.html
Hope this helps,
suzierose
Yes, I have heard of it.
Be on the lookout for MEK inhibitor therapy!
To date GEP identifies 7 types of multiple myeloma..MAF being one of them.
MAF is also identified as t14:16 (c-MAF), t(14,20) (MAF-B) and 8q24.3 (MAF-A)
MAF is found in 5-7% of all newly dx multiple myeloma cases and is associated with more aggressive multiple myeloma and shorter survival. Patients with MAF have significantly inferior survival when treated with hi-dose chemo and auto BSCT.
MAF is an oncogene that stimulates proliferation of multiple myeloma plus it increases interactions between multiple myeloma cells and stromal cells. It enhances proliferation and adhesion to bone marrow through activation of CCDN2 and integrin 7 genes. MAF genes are important to the malignant potential of multiple myeloma. MAF induces ARK-5 elevation. ARK-5 induces tumor invasion via IGF-1 elevation of AKt.
I do understand how all those alphabet descriptors can get quite confusing.
Avet Loiseau in Blood 2010 did challenge the negative prognosis and stated there was no difference in overall survival with t(14:16) based on a retrospective analyses of ~1K patients.
http://bloodjournal.hematologylibrary.org/content/117/6/2009.abstract
Recently Popovic noted (Feb 2011Blood) Annuziata et al (April 2010Blood) who identified a group of agents called MEK inhibitors as being effective vs. MAF.
http://bloodjournal.hematologylibrary.org/content/117/8/2396.abstract?ijkey=bcaa36f17c3606f3db0734cf148492b78434c690&keytype2=tf_ipsecsha
http://bloodjournal.hematologylibrary.org/content/117/8/2300.full
Did your FISH report identify a MAF translocation? Mine did.
So far, based on ASH2011 there seems to have been moderate success with the MEK inhibitor, selumetinib, in refractory multiple myeloma patients
http://ash.confex.com/ash/2011/webprogram/Paper42295.html
Hope this helps,
suzierose
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Maf gene
Wow suzierose, you know your stuff.
I am 23 days post stem cell transplant (auto) and I am 42.
According to my Onc the result of my FISH panel showed I was negative for the indicator that confirms poor prognosis, sorry cannot remember what gene that was but she said I had a missing Maf gene. I will be seeing my specialist on the 13 Feb to see how my STC has done so will question her in great detail then but I just wanted to get a bit of info to help me prepare questions.
Thanks again for info.
Michelle
I am 23 days post stem cell transplant (auto) and I am 42.
According to my Onc the result of my FISH panel showed I was negative for the indicator that confirms poor prognosis, sorry cannot remember what gene that was but she said I had a missing Maf gene. I will be seeing my specialist on the 13 Feb to see how my STC has done so will question her in great detail then but I just wanted to get a bit of info to help me prepare questions.
Thanks again for info.
Michelle
-
Meesh
Re: Maf gene
So Suzie, it's a translocation? I know my tests showed no translocations or deletions. I guess that means everything is good? I will ask.
Sorry to hear you have the MAF translocation. you sure know your stuff. This disease makes doctors of all of us doesn't it. At least research doctors.
-Chris
Sorry to hear you have the MAF translocation. you sure know your stuff. This disease makes doctors of all of us doesn't it. At least research doctors.
-Chris
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ninja performance - Name: Chris Hill
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: 08/04/2011
- Age at diagnosis: 43
Re: Maf gene
Hi Ninja!
Yes, Ninja...I would say you are in the 75% of multiple myeloma in the conventional group...excellent news for you!! Your future looks good and so do your overall outcomes....as you have experienced!!
and
Yes, again... it is a translocation.
That was a point I did not have clarity about until I read a few more articles and this one clinician presented a set of slides that connected the dots.
The slide divided multiple myeloma disease state by cytogentics and risk stratifications. First they showed that it is a 75-25% split for coventional vs high risk when multiple myeloma first presents.
After that, they showed which translocations were predominate in the coventional vs high risk multiple myeloma patients and further broke that down to what % of newly dx pts present with those cytogentic changes.
The biggest clarity came though because of how they labelled the chart.
The first column was headed chromosomal translocations..then the second column was headed genes dysregulated by those translocations. THAT was the missing piece. You have chromosomes that regulate genes!!!!..When the chromosome is translocated then specific genes are dysregulated. THAT gene dysregulation dictates/drives disease pathogenesis, i.e. the aggressiveness of the disease and/ or tumor invasion/burden as well as the survival prognosis.
These are the chromosomal translocations and the genes they dysregulate:
t (11;14) translocation dysregulates CCND1 (cyclin D1)
t(4:14)'''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''' FGFR-3 & MMSET
t(6;14) """""""""""""""""""""""""""""""""""" CCND3 (cyclin D3)
t(14;16) """""""""""""""""""""""""""""""""""" c-MAF
t(14;20) """"""""""""""""""""""""""""""""""" MAF-B
There are probably lots more hi-risk multiple myeloma chromosomal locations but these were the ones on her slides ...
Then she gave these FISH cytogenetic demographics, that overall 25% of multiple myeloma pts face hi risk abnormalities...along with the incidence of specific translocations in the newly diagnosed:
9% of newly dx are hypodiploidy
10% """""""""""""""" have del 17p
15% """""""""""""""""""''""" t(4;14)
5% """"""""""""""""""""""""" t(14;16)
6% """""""""""""""""""""""""''' PCLI>3%
14% """""""""""""""""""""""" del 13q
lol lol...about making doctors out of us....gotta tell you I think I have earned another PhD since this multiple myeloma diagnosis on 2 Sept....everything that was on my report I have delved into every crevice, nook and detail along with seeking out every single resource, written, webcasted or in a forum that I can find.
Knowledge is essential when it comes to knowing your choices. God only gives us one body!
Gotta make the most of it.
Thanks for caring2,
suzierose
Yes, Ninja...I would say you are in the 75% of multiple myeloma in the conventional group...excellent news for you!! Your future looks good and so do your overall outcomes....as you have experienced!!
and
Yes, again... it is a translocation.
That was a point I did not have clarity about until I read a few more articles and this one clinician presented a set of slides that connected the dots.
The slide divided multiple myeloma disease state by cytogentics and risk stratifications. First they showed that it is a 75-25% split for coventional vs high risk when multiple myeloma first presents.
After that, they showed which translocations were predominate in the coventional vs high risk multiple myeloma patients and further broke that down to what % of newly dx pts present with those cytogentic changes.
The biggest clarity came though because of how they labelled the chart.
The first column was headed chromosomal translocations..then the second column was headed genes dysregulated by those translocations. THAT was the missing piece. You have chromosomes that regulate genes!!!!..When the chromosome is translocated then specific genes are dysregulated. THAT gene dysregulation dictates/drives disease pathogenesis, i.e. the aggressiveness of the disease and/ or tumor invasion/burden as well as the survival prognosis.
These are the chromosomal translocations and the genes they dysregulate:
t (11;14) translocation dysregulates CCND1 (cyclin D1)
t(4:14)'''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''' FGFR-3 & MMSET
t(6;14) """""""""""""""""""""""""""""""""""" CCND3 (cyclin D3)
t(14;16) """""""""""""""""""""""""""""""""""" c-MAF
t(14;20) """"""""""""""""""""""""""""""""""" MAF-B
There are probably lots more hi-risk multiple myeloma chromosomal locations but these were the ones on her slides ...
Then she gave these FISH cytogenetic demographics, that overall 25% of multiple myeloma pts face hi risk abnormalities...along with the incidence of specific translocations in the newly diagnosed:
9% of newly dx are hypodiploidy
10% """""""""""""""" have del 17p
15% """""""""""""""""""''""" t(4;14)
5% """"""""""""""""""""""""" t(14;16)
6% """""""""""""""""""""""""''' PCLI>3%
14% """""""""""""""""""""""" del 13q
lol lol...about making doctors out of us....gotta tell you I think I have earned another PhD since this multiple myeloma diagnosis on 2 Sept....everything that was on my report I have delved into every crevice, nook and detail along with seeking out every single resource, written, webcasted or in a forum that I can find.
Knowledge is essential when it comes to knowing your choices. God only gives us one body!
Gotta make the most of it.
Thanks for caring2,
suzierose
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Maf gene
I am still confused as everything mentions translocation and dyregulation but what about deletion of the MAF Gene ?
I am slowly trying to understand all the info but it is hard.
I am slowly trying to understand all the info but it is hard.
-
meesh
Re: Maf gene
Dear Meesh,
A missing Maf gene is not the same thing as the translocation. In the case of the translocation, Maf is expressed at high levels. If one of two copies is deleted, it stands to reason that Maf expression will not be increased under those circumstances, I think you are OK in that regard.
A missing Maf gene could be an indicator of hypodiploidy, which is associated with higher risk disease. You may want to ask your oncologist if there is any evidence of hypodiploidy on your testing. However, if you have no other high-risk cytogenetic (chromosomal) abnormalities, I would not concern yourself with the Maf deletion.
I hope this helps!
Pete V.
A missing Maf gene is not the same thing as the translocation. In the case of the translocation, Maf is expressed at high levels. If one of two copies is deleted, it stands to reason that Maf expression will not be increased under those circumstances, I think you are OK in that regard.
A missing Maf gene could be an indicator of hypodiploidy, which is associated with higher risk disease. You may want to ask your oncologist if there is any evidence of hypodiploidy on your testing. However, if you have no other high-risk cytogenetic (chromosomal) abnormalities, I would not concern yourself with the Maf deletion.
I hope this helps!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: Maf gene
Dear Dr Voorhees,
Thank you so much for you message. I will ask this question of my multiple myeloma Dr at my next visit.
Thank you so much for you message. I will ask this question of my multiple myeloma Dr at my next visit.
-
Meesh
9 posts
• Page 1 of 1