Re: CD34 enumeration

From: Mike Keeney (Mike.Keeney@LHSC.ON.CA)
Date: Mon Jan 03 2000 - 15:08:50 EST


Dear Andrea,

In response to your questions:
1. which procedure is recommended these days?

2. which antibody is one supposed to use?  Are the ISEHAGE guidelines still recommending CD34-PE?


Back to your initial problem. Do you wash your samples after lysing? Most experts in the field now recommend no wash techniques.

Feel free to contact me directly if you wish followup on any of the points.

Good Luck!!

Mike Keeney
 


<<< "Andrea Illingworth" <dcdsflow@mint.net>  1/ 3  1:01p >>>
Dear flow group,

I am sure I am not the first one to observe this finding and my questions are :
1. which procedThere are several methods of enumerating CD34 commercially available
and the one you choose depends on your own specific requirements. The
IMAGN 2000 from BD is a microvolume fluorimeter (non flow based) method
which is perhaps the simplest to use. Recent report show good C.V.s on
blood and apheresis. Limitations are high C.V.s in low CD34 count range
(<10/ul)due to the limited volume analysed and as it is a single color
system the effect of low viabilty is undocumented.  The ProCount from BD
is a 3 color single platform method utilizing a vital dye on FL1, CD34PE
and CD45PerCp. The addition of TruCOUNT fluorospheres allows absolute
CD34 numbers to be derived directly from the flow cytometer. Published
studies also show good C.V.s for this method and the availabilty of an
automated algorithm may improve reproducibilty between sites. Limitations
are the inabilty to measure viabilty and because all 3 PMT's are used in
this method it is not possible to do CD34 subset analysis on a 3 color
laser. Apheresis packs with many platelet clumps may cause a problem for
the automated software, and a manual gating strategy using either ProCOUNT
or ISHAGE is available.  The StemKIT from Immunotech/Beckman-Coulter is
a 2 color CD45FITC CD34PE method that uses FlowCOUNT fluorospheres to
allow single platform CD34 absolute counts to be determined. Currently
gating is performed manually using the ISHAGE guidlines. An advantage of
this method is the ability to include 7-AAD in FL3 (or FL4) to assess
viabilty. Subsets of CD34 can also be determined by the addition of a
3rd antibody.  Recent reports from the European Working Group on Clinical
Cell Analysis show very good inter and intra laboratory C.V.'s with this
method.  For 2 color analysis CD34PE is the antibody of choice because
of its excellent signal/noise ratio. As long as class III antibodies of
CD34 are used FITC conjugates also work well. Other fluorochromes can
be used but each fluorochrome/antibody combination should be evaluated
before implementing in a clinical lab.  3. are most people just doing
the single parameter CD34 percentage or is the lineage-restricted vs
non-restricted %CD34 analysis becoming more important.  From the research
viewpoint there is tremendous interest in subsets of CD34. However most
clinical data published to date confirms that the single most important
factor predicting both short and long term engraftment is related to the
total number of CD34+/kg body weight infused into the patient.  Are the
absolute numbers as well as the percentages different? One or other method
may be causing a selective loss of a specific cell type.  How does the
other lab measure their CD34+ cells? It is safe to measure CD34 cells
without lysing in apheresis packs as the number of contaminating rbc's
is usually low. Simply resuspend the stained sample in 1ml of PBS before
analysis. This is not recommended for whole blood or cord blood due
to the very high number of red blood cells.  I hope this helps. Some
excellent references can be found in the Journal of Hematotherapy,
Transfusion and Clinical Cytometry. Many of the points you raised have
also recently been covered in Current Protocols in Cytometry by Jan
Gratama, Rob Sutherland and myself.  We are currently in the process
of evaluating a reliable procedure for CD34 enumeration.  We have been
sharing samples and comparing results with another institution and
have been surprised to find out in the process that lysed specimens
yield consistently higher percentages than unlysed specimens.  We have
been using the Coulter Stemkit which uses CD34-PE/CD45-FITC and their
designated lysing solution.  The other lab is using a no-lysis procedure
and a CD45-FITC/CD34-PerCP combination.  3. are most people just doing
the single parameter CD34 percentage or is the lineage-restricted vs
non-restricted %CD34 analysis becoming more important.
ure is recommended these days?
2. which antibody is one supposed to use?  Are the ISEHAGE guidelines still recommending CD34-PE?

Thanks for your help and have a happy and safe change into the new millennium!
Andrea Illingworth, MS, H(ASCP) 
Dahl-Chase Diagnostic Services
Flow Cytometry
333 State Street
Bangor, Maine 04401



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