Aplastic Anemia Research Center

This page includes my research prior to 2005.

Click here to access Active Research Blog.

Overview of This Page

I am convinced that there is a way to cure Aplastic Anemia and the answer lies in understanding why and how the immune system decides to attack immature cells.  Finding a cure will require the understanding of the various disciplines listed below and I will use this area of the site to store everything I am currently researching.  

I will constantly try to put everything into layman's terms.  My mission is to simplify, simplify, simplify!  People who constantly try to mystify this stuff are exactly like the computer professionals who try to keep people in the dark - the old mushroom theory (keep 'em in the dark and feed 'em shit).  Well, I refused to be kept in the dark in the world of data processing and I now refuse to be kept in the dark relative to my disease!

As a starting point, my initial bone marrow aspirate and smears revealed "mildly hypercellular marrow with mild hyperplasia or erythrocytic series and hypoplasia of megakaryocytes."  This means that my marrow has a slightly larger number of cells in a cross section of the marrow than is normal and an abnormal multiplication or increase in the number of normal cells with a lower number of megakaryocytes. Megakaryocytes are the giant polyploid  cells (the cells containing the genetic structure or chromosomes necessary for producing additional cells) of bone marrow that gives rise to 3-4,000 platelets each.  So in essence, I have a reduced number of the cells necessary to create platelets. 

If anyone reading this sees information that is incorrect or misinterpreted, please send me a note of correction. Thanks. 

BTW, much of my cursory research while I am traveling will now be at the forum.  It's easier to just send my comments there rather than opening and editing the website.

The Disciplines Involved

In addition to the obvious (clinical trials, treatment protocols and survivability), I am trying to understand the following disciplines as they relate to AA:

• Biology
• Immunology  Another Good Site for Immunology
• Immunopathology
• Biochemistry
• Hematology
• Microbiology
• Genetics and DNA Research
• Human Genome Project
• Multiple Chemical Sensitivities
• Alternative Medicines
• Nutrition and Allergies
• Stem Cells
• Pathophysiology

Other links on the links page. Which I will probably categorize at some point.

http://www.health.sa.gov.au/CanCare/REFERENC/Blood/Hemo/NetIt4/22020x.htm

How to Start - The Scientific Method

Above link is a good place to start by understanding how blood cells are produced.  Dr. Rea said that the biopsy from Strong said I had no Megakaryocytes (A megakaryocyte is the "progenitor" of platelets - one megakaryocyte produces 4000 platelets) present - That is a serious concern as Megakaryocytes is what produces platelets.  No Megakaryocytes, no platelet production!  I asked Sharon to send the biopsy results from Strong to EHCD.  

Nobody mentioned megakaryocytes to me until Dr. Rea came along.  Now I understand that my problem is more at the level of megakaryocytes than it is at the platelet level.  If I could keep my body from destroying megakaryocytes, it would then produce platelets???  Now that I think about it, Dr. Kirsher talked about "immature platelets" and he must have been referring to megakaryocytes (thank god somebody speaks english).

So now when I read Dr. Young's pathophysiology, it is beginning to make a little more sense.  As Richard Laughlin told me a long time ago, the key to understanding what you read is to not let a single word go by that you do not understand.  I literally have to look up every word in his report and then look up the words used to define what I looked up before the fog lifts.

I believe that each of these disciplines plays some part in developing a thorough understanding of the autoimmune and blood related illnesses.  It is a huge undertaking and I am being bombarded with new terminology in each discipline but I will be attempting to sort it out as I go and this is where it will start.  If you know anything about these areas and can help me sort it all out, please send me a note mailto:sales@aebiz.com.

Genetics Glossary - http://www.nhgri.nih.gov/DIR/VIP/Glossary/pub_glossary.cgi

1. Observe the situation
2. Ask a question
3. Turn that question into a testable hypothesis
4. Predict the outcome of your experiment
5. Perform your experiment
6. Analyze the results
7. Evaluate your hypothesis

Hematology Terms - Some Fundamentals Before we Ask the Questions

A Hematology Glossary

Red Cells, also known as erythrocytes, carry oxygen from the lungs to the tissues.

White Cells, also known as leukocytes, are responsible for killing any microorganisms that invade the body.

Platelets are small cellular particles produced in the bone marrow by shedding from very large cells called megakaryocytes and serve as the first line of prevention of bleeding when a blood vessel is damaged.

Anemia - Too few red blood cells in the bloodstream, resulting in insufficient oxygen to tissues and organs

Pancytopenia  Deficiency of all cell elements of the blood, aplastic anaemia.

hypoplastic anaemia  A low red blood cell count that results from the underproduction of red blood cells by the bone marrow. This is often secondary to a drug (chemotherapy) side effect.

thrombocytopenia  A decrease in the number of platelets in the blood, resulting in the potential for increased bleeding and decreased ability for clotting.

granulocytopenia  A reduced number of white blood cells in the circulation.

leukopenia Abnormal decrease in the number of white blood cells.

Polycythemia is the term used to designate overproduction of red cells, white cells and platelets.

Erythrocytosis is the term used to designate the overproduction of red cells alone.

Leukocytosis is the term used to designate overproduction of white cells alone.

Thrombocytosis (or thrombocythemia) is the term used to designate overproduction of platelets alone

Myelofibrosis is the term used to designate an increase in the fibrous tissue of the bone marrow. Myelofibrosis is not a primary process but is always caused by another disorder.

Hematopoietic Progenitor Cells are the parent cells in the bone marrow for red cells, white cells and megakaryocytes. The most primitive hematopoietic progenitor cells are multipotent and give rise to the progenitor cells for red cells, white cells and megakaryocytes.

Myeloproliferative Disease is the term used to define a disease arising in a hematopoietic progenitor cell that results in the uncontrolled (autonomous) overproduction of normal-appearing blood cells in the absence of an appropriate stimulus such as lack of oxygen for red cells, lack of microbial invasion or inflammation for white cells and lack of bleeding for platelets.

Idiopathic (or Essential) is a term used to indicate that the cause for a disease process or disorder is unknown

Clonal is a term used to describe diseases arising from a single cell.

Cytogenetics is a technique used to analyze the number and integrity of a cell's chromosomes

Bone Marrow Aspirate is a technique, similar to drawing blood, for obtaining bone marrow for microscopic examination, cytogenetics and flow cytometry.

Bone Marrow Biopsy is a technique by which a piece of bone containing marrow is obtained when marrow cannot be aspirated to identify the presence of myelofibrosis, and to assess marrow cellularity and architecture.

Flow Cytometry is a technique by which individual blood or marrow cells can be analyzed for clonality.

Uric Acid is a by-product of DNA that can accumulate and cause kidney stones or gouty arthritis if the white count is high or if white cells are being rapidly destroyed by chemotherapy.

Phlebotomy is the removal of blood from a vein to reduce the number of red cells and induce iron deficiency to slow their reaccumulation.

The Questions

I am beginning to believe that what will be most important in my battle is clearly asking the right questions and then researching the answers, so here are some questions I am working:

In acquired aplastic anemia, clinical and laboratory observations suggest that this is an autoimmune disease.  http://aplasticcentral.com/aplastic_facts.htm

Ongoing reading but some fundamentals - At a cellular level, the immune system is charged with remembering microorganisms that are causing problems and develops antigens to destroy these rogue microorganisms.  If the blood cells become targets of the immune system (or apoptosis which is programmed death of unnecessary cells), then the blood cells are in trouble because the immune system is very good at what it does - protect the body from microorganisms it doesn't like (It even remembers that you had chicken pox as a kid and if any small pox like microorganisms show up it destroys them) 

3. What exactly is happening when the lymphocytes attack the immature platelets and how can I follow that thread to understand the immune system malfunctioning - what is Dr. Rea doing to stimulate platelet growth? 

Lymphocytes are responsible for fighting infections and it appears that in Aplastic Anemia, our lymphocytes have decided that the progenitor cells are an infection?  There must be some connection between the fact that I am low in protein and CD34 is a "glycoprotein.

4. Better yet - make sure I understand in detail lymphocytes, CD34 and T cells and apoptosis, etc. and then formulate the questions.

Thanks to Kenton, gaining a much better understanding, but still have a ways to go.

http://www.bioscience.org/news/scientis/apoptos.htm has a good discussion of apoptosis vs. tumor necrosis factor (TNF) apoptosis involves a single cell. TNF involves a group of cells. 

5.How does environmental illness and MCS relate to Aplastic Anemia?

Best guess so far (9/30/01) is that in addition to inheriting a pre-dispositon to an autoimmune disease, my body's immune system began to malfunction as a result of being continually exposed to a series of viruses (shingles, menangitis) and toxins (pesticides, mercury, paint, fertilizer, varnishes, molds).  If we can isolate the causes by testing what my body may react to, we can  prepare and inject antigens to correct the imbalance.  At the same time, I do the physical therapy (exercise, sauna, vitamins and massage) to rid my body of toxins -so far, it appears to be working.  I am also eating a restrictive diet and taking a large number of vitamins and supplements designed to reset my body's immune system.  

6. So what are these CD34 things anyway and how do they interact with everything else we know?

See Kenton's Research.

7. What is the difference between leukocytes and lymphocytes?

A leukocyte is any kind of White Blood Cell.  A lymphocyte is a specific type of WBC in the lymphatic system (The tissues and organs (including the bone marrow, spleen, thymus and lymph nodes) that produce and store cells that fight infection and the network of vessels that carry lymph.)  So - lymphocytes are part of the immune system that fight infections. (how can they keep saying that hodgkins and AA are unrelated??????)

8. I don't understand the fact that if my immune system is over-reacting, why I want to "strengthen" my immune system. As Sue explains it, my immune system is out of balance and the EI strategy is designed to get it back in balance.  Need to further articulate this in a way that I understand.

According to Docs (Lancet and Rea) what I need to do is "balance" my immune system and so far I think the MCS/environmental approach appears to have a better/less toxic way of doing this.

9. Define, rationalize, categorize, synthesize and understand cytoxins, cytokines, proteins, amino acids, CD's, folic acid, interleukins, lymphocytes, leukocytes, toxins, antibodies, antigens, magnesium, calcium, hemoglobin, hematocrits, phagocytosis, neutropenia, thrombocytopenia, T Cells, B Cells, Killer T Cells, apotosis, fibromyalgia, immune system, thymus, tonsils, adenoids, spleen, allergies as related to immune disorders, CFS (Chronic Fatigue Syndrome, MCS (Multiple Chemical Sensitivities), detoxification vs chelation, depuration, mitosis, vitamins (B12, E, C, A), L-Lysine, Cod Liver Oil, seratonin, glycoprotein, lymphatic system vs lymphocytes vs lymph nodes?

Cytokines are chemical messengers that activate the immune system.

10. Why do all these other diseases keep popping up and what is the relationship with AA: AIDS, HIV, Arthritis, Lupus, Hodgkins, TTP, ITP, MDS-RA, CFS, MCS, Diabetes.  

They are all related to the immune system.  If you start by getting the immune system in  balance (see above) then you can begin to address the specific issue that got your immune system out of whack in the first place.  I question why everyone (and especially NIH) fails to recognize the similarities and have a centralized autoimmune effort going on rather than all the fractionalized efforts.  It sucks that HIV gets all the attention when you consider how most people become infected in the first place and by the way I live in fear of one of my almost 100 transfusions passing HIV or hepatitis or some other ugly disease on to me.

Specific difference between AA and ITP courtesy of Kenton:

ITP involves the direst attack on the platelets.  In AA the low
platelet counts are due to the lack of production (maybe in
combination with direct attack) of the platelets.  I a platlet
transfusion was given to someone w/ ITP the platelets would be
marked with antibodies and subsequently destroyed.  So
transfusions are not effective at combatting ITP.  In AA it seems
that the precursor cells to platelts (and other blood cells) are
attacked and decreased in number.  This causes less of these
cells to be present in the body because there is nothing left to
make them.  It seems thaat splenectomy is a common and effective
(though somewhat radical) treatment for ITP.  This gets rid of
the problem (the spleen is involved in the removal of blood cells
from the body) but still does not give us a cause, Why is the
spleen misbehaving?  According to the article that you sent me
there are numerous causes with a similar result (ITP).  In my
mind these should all be considered different diseases, this
would simplify the diagnosis and perhaps aid in the treatment.
The disease could be grouped by common cause and the effective
treatment for each cause could be systematically tried.  There is
no use trying to combat a genetically induced form of ITP with a
treatment that is more consistantly effective at combatting viral
or environmentally induced ITP.  Keep in mind that the body is
incredibly complex at the biochemical and molecular level and the
substitution or deletion of just one enzyme in different
metabolic processes might lead to the same result even though the
difference isn't even related.  The same can be and is true for
proteins or sugars (riboses) in DNA at the molecular level.  One
small difference can make a huge impact on the function of a
gene.  All because two people have the same symptoms it doesn't
mean that they have a disease originating from the same cause.  I
hope that this answers your question about the difference between
AA and ITP.  I'm sending the web site from NIH, you've probably
already been there but it seems generic enough to understand.
Another interesting note about ITP is the reference to anti-D
immunoglobin.  This is another antibody (biologic) that is
involved in Rh recognition and desensitization.  The
effectiveness of this treatment makes me point toward differences
in Rh complexes present on the platelet cells.  Kind of like I
thought CD34 in your AA, as compared with others AA that might be
affected by other receptors.  The fact that the platelets are
marked by the antibodies that result in the removal of the cells
indicate to me that the spleen is not malfunctioning and that the
cells that are marking the cells for destruction are the problem
(usually B-cells) but I do not know the mechanism that the spleen
uses for removal of the cells.  Something more for me to look up,
in any cae I would have to say that the removal of the spleen is
probably the removal of a healthy organ in most cases of ITP.
Let me know if anything I said contradicts any info. that you
have.  This helps rule out some ideas and bring others to the
forefront.  Also let me know if I can be of anymore help.

http://www.niddk.nih.gov/health/hematol/pubs/itp/itp.htm

11. Dr. Rea had me take seratonin to guard against platelet reaction and it seemed to work.  Why?  Seratonin is a major component of platelets?  What is seratonin?

The Details and My Attempt to Decipher  

(In Aplastic Anemia) ... Morphologically, the bone marrow is devoid of hematopoietic (blood cell formation) elements, showing largely fat cells. Flow-cytometry shows that the CD34 (CD34 is a transmembrane glycoprotein constitutively expressed on endothelial cells and on hematopoietic stem cells. This highly O-glycosylated molecule, containing serine and threonine-rich mucin like domains, binds to L-selectin, but its functional capacity in non-lymphatic venules is uncertain. Studies have suggested that CD34 is important in tethering lymphocytes.  - WHAT THE HELL DOES THAT MEAN?????

Mice deficient in CD34 exhibited no detectable abnormalities in postsurgical leukocyte rolling in cremaster venules. Antibodies blocking L-selectin function reduced rolling in CD34 deficient mice suggesting that CD34 lacks major significance as a ligand for L-selectin. The endothelial ligands for L-selectin are currently unknown.)   MY GOD - WHY DON'T THEY SPEAK ENGLISH!!! cell population, which contains the stem cells and the early committed progenitors, is significantly reduced. In vitro colony culture assays suggest profound functional loss of the hematopoietic progenitors, so much so that they are unresponsive even to very high levels of hematopoietic growth factors.  Our bone marrow is deficient in the vital cells that ultimately produce platelets, WBC's and RBC's (progenitors).

Little evidence points to a defective microenvironment as a cause of aplastic anemia. In patients with severe aplastic anemia, the stromal (Connective tissue cells of an organ found in the loose connective tissue) cell function is normal, including growth factor production. Adequate stromal function is implicit in the success of marrow transplantation in aplastic anemia because frequently the stromal elements remain of host origin.

The role of an immune dysfunction was suggested in 1970, when autologous recovery was documented in a patient with aplastic anemia who had failed to engraft after marrow transplantation; Mathe proposed that the immunosuppressive regimen used for conditioning promoted the return of normal marrow function. Subsequently, numerous studies have shown that in approximately 70% of patients with acquired aplastic anemia, immunosuppressive therapy improves marrow function. Immunity is regulated genetically (by immune response genes) and also influenced by environment (eg, nutrition, aging, previous exposure). Although the inciting antigens that breach immune tolerance with subsequent autoimmunity are unknown, human leukocyte antigen (HLA)-DR2 is over-represented among European and American patients with aplastic anemia.

Suppression of hematopoiesis (formation and development of blood cells) likely is mediated by an expanded population of cytotoxic T lymphocytes: cluster of differentiation 8, HLA-DR+ (CTLs: CD8, HLA-DR+), which are detectable in both the blood and bone marrow of patients with aplastic anemia. These cells produce inhibitory cytokines, such as gamma interferon and tumor necrosis factor, which are capable of suppressing progenitor cell growth. (The T lymphocytes are killing the progenitors!) These cytokines suppress hematopoiesis by affecting the mitotic cycle (cell division) and cell killing (apotosis) through induction Fas (Fas is a known inducer of apoptosis and is important in the regulation of several aspects of the immune system, including cytotoxic killing of cells potentially harmful to the organism such as virus-infected or tumor cells.)-mediated apoptosis (Programmed cell death) It also has been shown that these cytokines induce nitric oxide synthase and nitric oxide production by marrow cells, which contributes to immune-mediated cytotoxicity (The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitised T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement) and elimination of hematopoietic cells.

Anemia is a disorder that results in a decrease in the ability of the blood to carry oxygen. Anemia is itself not a diagnosis but merely a sign of underlying disease. The initial classification of anemia is best accomplished by examination of the data from a hematology analyzer and by an examination of the peripheral blood smear. The physician most commonly classifies anemias initially by the instrument's red cell indicies, especially the mean corpuscular volume (MCV). On newer counters, the red cell distribution width (RDW) or red cell morphology index (RCMI) is another useful measurement. The anemia may be microcytic, normocytic, or macrocytic.

Additional Definitions, Glossaries and Revelations

MACROCYTIC ANEMIA

Macrocytic anemias are less commonly encountered than normocytic or microcytic anemias. These anemias may be caused by marrow failure such as aplastic anemia and myelodysplasis, or caused by deficiencies of vitamin B12 or folic acid; or caused by autoimmune hemolysis or cold agglutinins.

Myeloid Stem Cell
Produced by the pluripotent
stem cell. It will eventually
mature into red or white blood
cells or platelets.

Lymphoid Stem Cell
Produced by the pluripotent
stem cell. It will mature into
a T cell or a B cell

Hematopoiesis
The formation and development of
blood cells

Red Blood Cell (Erythrocyte)
Contains haemoglobin which
carries oxygen. Lives for 120
days

Platelets (Thrombocytes)
Helps to control bleeding
by clotting blood at sites of
injury. Lives for 5 - 9 days.

Neutrophil
A white blood cell that
engulfs and kills
bacteria

Macrophage
A white blood cell that
engulfs and kills
bacteria

Monocyte
Travels to areas of
infection where it
becomes a macropahge

Eosinophil
Kills parasitic worms
and removes bacteria

Basophil
Intensifies and hastens
the immune response
to infection

Mast Cell
Similar to a basophil but
found in tissue instead of
blood

B Cell
Produces plasma cells

Plasma Cell
Makes antibodies
which recognize and kill
infections

T Cell
Kills infections directly and
stimulates B cells to produce
antibodies

Myeloblast
Immature cell which
eventually becomes a white
blood cell

B Lymphoblast
Immature B cell

T Lymphoblast
Immature T cell

Monoblast
Immature monocyte

Megakaryocyte
One megakaryocyte
produces 4000 platelets

Megakaryoblast
An immature
megakaryocyte

Proerythroblast
An immature red blood
cell

Myeloblast
Immature cell which
eventually becomes a white
blood cell

Myeloblast
Immature cell which
eventually becomes a white
blood cell

White blood cells, depending
on type of cell, it may live for
a few hours or a few years

Pre B Cell
Immature B cell

Prothymocyte
Immature T cell

Hematocrit

• What is the hematocrit?
• How is the hematocrit measured?
• What is a normal hematocrit?
• What does a low hematocrit mean?
• What does a high hematocrit mean?

What is the hematocrit?

The hematocrit is the proportion, by volume, of the blood that consists of red blood cells. The hematocrit (hct)is expressed as a percentage. For example, an hematocrit of 25% means that there are 25 milliliters of red blood cells in 100 milliliters of blood.

How is the hematocrit measured?

The hematocrit is typically measured from a blood sample by an automated machine that makes several other measurements at the same time. Most of these machines in fact do not directly measure the hematocrit, but instead calculate it based on the determination of the amount of hemoglobin and the average volume of the red blood cells. The hematocrit can also be determined by a manual method using a centrifuge. When a tube of blood is centrifuged, the red cells will be packed into the bottom of the tube. The proportion of red cells to the total blood volume can be visually measured.

What is a normal hematocrit?

The normal ranges for hematocrit are dependent on age and, after adolescence, the sex of the individual. The normal ranges are:

• Newborns: 55-68%
• One (1) week of age: 47-65%
• One (1) month of age: 37-49%
• Three (3) months of age: 30-36%
• One (1) year of age: 29-41%
• Ten (10) years of age: 36-40%
• Adult males: 42-54%
• Adult women: 38-46%

These values may vary slightly between laboratories.

What does a low hematocrit mean?

A low hematocrit is referred to as being anemic. There are many reasons for anemia. Some of the more common reasons are loss of blood (traumatic injury, surgery, bleeding colon cancer), nutritional deficiency (iron, vitamin B12, folate), bone marrow problems (replacement of bone marrow by cancer, suppression by chemotherapy drugs, kidney failure), and abnormal hematocrit (sickle cell anemia).

What does a high hematocrit mean?

Higher than normal hematocrit levels can be seen in people living at high altitudes and in smokers. Dehydration produces a falsely high hematocrit that disappears when proper fluid balance is restored. Some other infrequent causes are lung disease, certain tumors, a disorder of the bone marrow known as polycythemia rubra vera, and abuse of the drug erythropoietin (Epogen) by athletes for blood doping purposes.

What is Apotosis?  (Cell Biology)

Chart below shows what Roche Diagnostics know about apoptosis (physiologically regulated cell suicide).  In Aplastic Anemia, our immune system causes premature apoptosis. Apoptosis is the opposite of necrosis - cell death by accident.  Further information on apoptosis including a clickable version of the chart can be found at http://biochem.roche.com/prodinfo_fst.htm?/apoptosis/

I'm pretty sure that understanding CD34 and how it relates to the immune system, protein status and amino acids is critical to finding the immune system linkage I am looking for, but look at this and tell me what it means!?

ALTERNATE NAMES FOR CD34  

• CD34 [HUGO gene name]
• gp105-120

MAJOR LINKS FOR CD34  

• NCBI LocusLink Record: 947
• Mendelian Inheritance in Man (OMIM): 142230
• SwissProt annotated protein record: P28906

CELLULAR FUNCTION OF CD34 Link to additional info in FORUM  

• Cell-cell adhesion
• Inhibition of hematopoietic differentiation?

DISEASE RELEVANCE OF CD34 AND FUNCTION OF CD34 IN INTACT ANIMAL  

• No abnormality in leukocyte trafficking was detected in the CD34 knock-out mice
• In 1 of 2 reports of CD34 knock-out mice, a decrease in hematopoietic progenitors was found in the knock-out mice
• Utilization of CD34 mAb to quantitate and purify lymphohematopoietic stem / progenitor cells for research and for clinical bone marrow transplantation

• Families in which CD34 is a member
  • CD34-->sialomucin-->Mucins

MOLECULAR STRUCTURE OF CD34  

• A heavily glycosylated type I transmembrane protein. There are two forms of the CD34 protein, resulting from alternative splicing
• The complete extracellular region is present in both forms of CD34
• There is a cysteine-rich repeat (Ig-like domain) in the extracellular region
• The full-length form of CD34 molecule has an intracellular domain, which contains consensus sites for protein kinase C (PKC) phosphorylation, serine and threonine phosphorylation by other kinases, and tyrosine phosphorylation (To date, only serine phosphorylation by has been actually demonstrated)
• The truncated form of CD34 lacks most of the intracellular domain, including many of the potential phosphorylation sites

  	Full-length form	Truncated form
  Full amino sequence	385	328
  Intracellular region	73	16
  Transmembrane	23	23
  Extracellular region	258	258
  Signal sequence	31	31

MOLECULAR MASS OF CD34  

POST-TRANSCRIPTIONAL MODIFICATION OF CD34  

• One species contains exons 1 through 8 and forms the full-length form of CD34
• An alternative splice variant results in the insertion of an additional exon (exon X, 194bp) between exon 7 and 8; this introduces a translational stop codon, which results in the truncated form of CD34 with a shorter cytoplasmic domain
• The transmembrane and extracellular regions of both forms of CD34 are identical

POST-TRANSLATIONAL MODIFICATION OF CD34  

• Beginning at the NH2 terminus, the extracellular domain is heavily N- and
• O-sialoglycosylated
• Serine phosphorylation of the intracellular domain has been demonstrated, and there are potential sites for serine, threonine, and tyrosine phosphorylation

SUBSTRATES FOR CD34   - No information

ENZYMES WHICH MODIFY CD34   - No information

LIGANDS FOR CD34 AND MOLECULES ASSOCIATED WITH CD34  

• Expressed on early lymphohematopoietic stem and progenitor cells, small-vessel endothelial cells, embryonic fibroblasts, and some cells in fetal and adult nervous tissue
• Also, expressed on hematopoietic progenitors derived from fetal yolk sac, embryonic liver, and extra-hepatic embryonic tissues including aorta-associated hematopoietic progenitors in the 5 week human embryo

SELECTION OF OTHER CD34-SPECIFIC REFERENCE MAB