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Hi Marcos,

Thanks for the great sites. I've never seen the " hierarchy " of blood

cells so clearly put before. You didn't happen to come across anything

definitive regarding how many HSC's we have did you?

Those diving pictures were pretty neat too. Some were nothing short of

spectacular while others were amusingly creepy :) Thanks for sharing

them.

Tracey

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can you send me the pictures to, i would love to see them

>From: " Tracey " <traceyincanada@...>

>Reply-

>

>Subject: [ ] Re: blood cell chart and vacation from statistics

>Date: Tue, 12 Jun 2007 01:12:09 -0000

>

>Hi Marcos,

>

>Thanks for the great sites. I've never seen the " hierarchy " of blood

>cells so clearly put before. You didn't happen to come across anything

>definitive regarding how many HSC's we have did you?

>

>Those diving pictures were pretty neat too. Some were nothing short of

>spectacular while others were amusingly creepy :) Thanks for sharing

>them.

>

>Tracey

>

>

>

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Hi Tracey,

Not a total number. Below is a link to the most complete overview

article on HSCs I have in my bookmarks, but I hadn't the time to go

over it today. If my memory is correct it says the picture is more

complex that just one kind of HSC. There are long term stem cells and

short term stem cells. And we have to keep in mind the subject is

still far from being well understood. It says somewhere that about

1/10000 to 1/15000 cells in the bone marrow are long term blood stem

cells, and I think those are the ones we care about. So if you find

somewhere the number of cells in the bone marrow you may have the

solution. I have read this a few months ago so I am a bit foggy, but

there's a lot of informations in this paper.

Here's the article :

http://tinyurl.com/27r7qd

Cheers,

Marcos.

On 6/11/07, Tracey <traceyincanada@...> wrote:

> > Hi Marcos,

>

> Thanks for the great sites. I've never seen the " hierarchy " of blood

> cells so clearly put before. You didn't happen to come across anything

> definitive regarding how many HSC's we have did you?

>

> Those diving pictures were pretty neat too. Some were nothing short of

> spectacular while others were amusingly creepy :) Thanks for sharing

> them.

>

> Tracey

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Hi Marcos,

Thanks for the great link. I just skimmed it and it looks very

informative. I'm loooking forward to reading it in more depth.

Take care,

Tracey

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Hi Tracey, Marcos, et al,

The following is taken from an article in Acta Hematologia 2004 - Minimal

Residual Disease in Hematological Malignancies.

" However, the heterogeneity of the preanalytical environment of PCR machines

and methods, and of the methods to calculate the final results causes

confusion among patients, treating physicians and laboratories. The

universal acceptance of real-time PCR urgently demands standardization of

nomenclature and technologies. At present, at least seven different systems

are commercially available using three different methods of fluorescence

labeling [2]. However, adjustment of the protocols, standardization of

preanalytical considerations and of the methods to calculate the final

transcript ratio should result in comparable data. "

I know that there is more than one effort underway to standardize RT-PCR

testing and reporting. It looks like it will take years before this is

resolved.

The best we can do is to find a lab that produces consistent results and

stick with it.

Zavie

Re: [ ] Re: blood cell chart and vacation from statistics

Hi Tracey,

Not a total number. Below is a link to the most complete overview

article on HSCs I have in my bookmarks, but I hadn't the time to go

over it today. If my memory is correct it says the picture is more

complex that just one kind of HSC. There are long term stem cells and

short term stem cells. And we have to keep in mind the subject is

still far from being well understood. It says somewhere that about

1/10000 to 1/15000 cells in the bone marrow are long term blood stem

cells, and I think those are the ones we care about. So if you find

somewhere the number of cells in the bone marrow you may have the

solution. I have read this a few months ago so I am a bit foggy, but

there's a lot of informations in this paper.

Here's the article :

http://tinyurl.com/27r7qd

Cheers,

Marcos.

On 6/11/07, Tracey <traceyincanada@...> wrote:

> > Hi Marcos,

>

> Thanks for the great sites. I've never seen the " hierarchy " of blood

> cells so clearly put before. You didn't happen to come across anything

> definitive regarding how many HSC's we have did you?

>

> Those diving pictures were pretty neat too. Some were nothing short of

> spectacular while others were amusingly creepy :) Thanks for sharing

> them.

>

> Tracey

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That would be a nice thing indeed. Looking around it's possible to find the

operation manuals for the brc-abl PCR tests in some of the labs. It is not

only that the procedures vary from one lab to the other, but also that

accurate results are dependent on very fine control of parameters like

temperature or delay between the blood draw and the actual measures. I get

my blood taken at a small hmo hospital nearby that sends it to the big hmo

hospital 20mi away, that sends it to Stanford Hospital, across the street

from my office. Efficiency at work ;)

But even if I can't trust these numbers to be consistent with other tests, I

want at least to have some idea of how they are obtained and what they are

supposed to measure. It's all part on trying to understand better our bug.

Know the enemy and Pay attention to detail where familiar sounds during my

education.

Marcos.

On 6/12/07, Zavie miller <zmiller@...> wrote:

>

>

> Hi Tracey, Marcos, et al,

>

> The following is taken from an article in Acta Hematologia 2004 - Minimal

> Residual Disease in Hematological Malignancies.

>

> " However, the heterogeneity of the preanalytical environment of PCR

> machines

> and methods, and of the methods to calculate the final results causes

> confusion among patients, treating physicians and laboratories. The

> universal acceptance of real-time PCR urgently demands standardization of

> nomenclature and technologies. At present, at least seven different

> systems

> are commercially available using three different methods of fluorescence

> labeling [2]. However, adjustment of the protocols, standardization of

> preanalytical considerations and of the methods to calculate the final

> transcript ratio should result in comparable data. "

>

> I know that there is more than one effort underway to standardize RT-PCR

> testing and reporting. It looks like it will take years before this is

> resolved.

>

> The best we can do is to find a lab that produces consistent results and

> stick with it.

>

> Zavie

>

>

>

>

> Re: [ ] Re: blood cell chart and vacation from statistics

>

> Hi Tracey,

> Not a total number. Below is a link to the most complete overview

> article on HSCs I have in my bookmarks, but I hadn't the time to go

> over it today. If my memory is correct it says the picture is more

> complex that just one kind of HSC. There are long term stem cells and

> short term stem cells. And we have to keep in mind the subject is

> still far from being well understood. It says somewhere that about

> 1/10000 to 1/15000 cells in the bone marrow are long term blood stem

> cells, and I think those are the ones we care about. So if you find

> somewhere the number of cells in the bone marrow you may have the

> solution. I have read this a few months ago so I am a bit foggy, but

> there's a lot of informations in this paper.

>

> Here's the article :

> http://tinyurl.com/27r7qd

>

> Cheers,

> Marcos.

>

> On 6/11/07, Tracey <traceyincanada@... <traceyincanada%40>>

> wrote:

> > > Hi Marcos,

> >

> > Thanks for the great sites. I've never seen the " hierarchy " of blood

> > cells so clearly put before. You didn't happen to come across anything

> > definitive regarding how many HSC's we have did you?

> >

> > Those diving pictures were pretty neat too. Some were nothing short of

> > spectacular while others were amusingly creepy :) Thanks for sharing

> > them.

> >

> > Tracey

>

>

>

>

>

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Hi Zavie,

I don't think the issue is about the standardization of PCR testing

(although that is an issue, just not the one we were discussing at

the moment).

The issue that I'm interested in is this; although our FISH and BMB

tests on diagnosis would have us believe that every single one of our

stem cells is leukemic (or at least more than 95% of them), I

personally don't believe this to be the case because I don't feel

that a sample of 20 or 200 cells is representative of all the stem

cells we have. This is the issue that Marcos and I have been batting

around as he believes the BMB and FISH ARE representative of the

whole picture.

Now we know that on diagnosis we have about one trillion hematoietic

stem cells that are leukemic so the question remains how many HSC's

in total do we have? If we knew that, we could make a general

statement about what percentage the 1 trillion represents.

I found a number of sites that said the turn over rate of HSC's is

about 1 trillion a day which leads me to believe that we must have

far more than a trillion to start with if that many are turning over

every day. Is this a logical assumption or am I missing something?

Here is one of the sites that mentioned the 1 trillion turn over rate:

http://www.lub.lu.se/luft/diss/med_853/med_853.pdf

Tracey

> > > Hi Marcos,

> >

> > Thanks for the great sites. I've never seen the " hierarchy " of

blood

> > cells so clearly put before. You didn't happen to come across

anything

> > definitive regarding how many HSC's we have did you?

> >

> > Those diving pictures were pretty neat too. Some were nothing

short of

> > spectacular while others were amusingly creepy :) Thanks for

sharing

> > them.

> >

> > Tracey

>

>

>

>

>

>

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> I found a number of sites that said the turn over rate of HSC's is

> about 1 trillion a day which leads me to believe that we must have

> far more than a trillion to start with if that many are turning

over

> every day. Is this a logical assumption or am I missing something?

Tracey

Thank you for digging up that article. However, I believe that you

may have interpreted that sentence on turnover rate a bit

incorrectly. The author's wording refers to a turnover rate of a

trillion cells of the hematopoietic system and this would include all

the white and red blood cells.

I beleive that the most current hypothesis is that the HSC in the

marrow space under normal conditions do not turnover at all.

However, this statement is really a matter of semantics. The HSC can

divide and when it does, one of the resulting cells (progenitor)

commits itself to moving up the path (see Marcos chart). The other

half of the divison retains the properties of the HSC. Also, keep in

mind as one looks at the chart that as the progenitor is moving up

the path to one of the cell lineages (i.e.neutrophil), it is both

maturing and replicating itself. I don't know the exact number but a

single progenitor cell can result in thousands of fully mature blood

cells.

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This is a very tricky field so take what I write with some healthy dose of

sketicism :

Here a few things I THINK I understood :

- HSCs have both the capacity of self renewing by dividing in to

two HSCs, or to differenciate by dividing into two cells that are more

specialized (myeloid or lymphoid progenitors, which will keep commiting

towards more mature blood cells). But when they divide both new cells are of

the same kind. The type of division (self renew or differenciation) depends

on messengers or context.

- The article I gave a link says somewhere that in average 8% of the normal

HSCs are dividing at the same time. But that can vary in fonction of demand.

Cheers,

Marcos.

On 6/12/07, <timothyfarley16@...> wrote:

>

>

> > I found a number of sites that said the turn over rate of HSC's is

> > about 1 trillion a day which leads me to believe that we must have

> > far more than a trillion to start with if that many are turning

> over

> > every day. Is this a logical assumption or am I missing something?

>

> Tracey

>

> Thank you for digging up that article. However, I believe that you

> may have interpreted that sentence on turnover rate a bit

> incorrectly. The author's wording refers to a turnover rate of a

> trillion cells of the hematopoietic system and this would include all

> the white and red blood cells.

>

> I beleive that the most current hypothesis is that the HSC in the

> marrow space under normal conditions do not turnover at all.

> However, this statement is really a matter of semantics. The HSC can

> divide and when it does, one of the resulting cells (progenitor)

> commits itself to moving up the path (see Marcos chart). The other

> half of the divison retains the properties of the HSC. Also, keep in

> mind as one looks at the chart that as the progenitor is moving up

> the path to one of the cell lineages (i.e.neutrophil), it is both

> maturing and replicating itself. I don't know the exact number but a

> single progenitor cell can result in thousands of fully mature blood

> cells.

>

>

>

--

Marcos Perreau Guimaraes

Suppes Brain Lab

Ventura Hall - CSLI

Stanford University

220 Panama street

Stanford CA 94305-4101

650 329 9920 x 305

650 630 5015 (cell)

marcospg@...

montereyunderwater@...

www.stanford.edu/~marcospg/

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>

> This is a very tricky field so take what I write with some healthy

dose of

> sketicism :

> Here a few things I THINK I understood :

> - HSCs have both the capacity of self renewing by dividing in to

> two HSCs,

That is correct. Some consider the HSC to be essentialy " immortal " .

or to differenciate by dividing into two cells that are more

> specialized (myeloid or lymphoid progenitors, which will keep

commiting

> towards more mature blood cells). But when they divide both new

cells are of

> the same kind.

You are right that they basically " commit " to a cell lineage. I

believe that the best evidence is that after a division, one cell

retains the HSC characteristics and returns to a resting state. The

other cell then reponds to the needs of the body and begins going

down a path and eventually become thousands of a single type of a

mature blood cell.

The type of division (self renew or differenciation) depends

> on messengers or context.

Also correct.

A lot of studies on the HSC came from Irv Weissman's lab at your

institution (Stanford).

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