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Can Honeybees Lead To A Better Treatment For Myelodysplastic Syndromes?

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Published: Mar 22, 2013 9:45 am
Can Honeybees Lead To A Better Treatment For Myelodysplastic Syndromes?

Honeybees have a fantastic story, one that may provide insight into myelodysplastic syndromes, aging, and a number of other conditions.

The drones and worker bees exist to work. Their various jobs include nursing the ever-hatching brood, visiting flowers to bring back nectar, constructing wax combs, serving as cleaners and guards for the hive, and literally living to serve the queen.

The queen bee, on the other hand, looks different and is larger than the other bees. She is fed and groomed by a hoard of attendants, does not work a day in her life, and her only job is to lay eggs that can amount to as many as 2,000 on a good summer day. She produces a pheromone called “queen substance” that informs the colony that a viable queen is present.

The greatest difference between the queen and her subjects, however, is that the workers have a life span of two to four weeks while the queen can live up to eight years.

The real kicker is that drones and the queen bee share the exact same set of genes. What accounts for the dramatic physical differ­ences is therefore not the genes but their relative expression (i.e., how much of each gene’s corresponding protein the body makes).

In the case of bees, it seems that the diet they are fed as larvae and beyond controls which genes are turned on to be translated into protein. Bees’ rich and nutritious diet, called royal jelly, is produced in the mouth glands of nursing bees and fed to all hatching larvae; however, the workers are soon weaned off the royal jelly and given nectar and pollen, while the queen bee is bathed in the royal jelly into adulthood.

What is the magic substance in royal jelly? Phenyl butyrate. Here is how it works:


Click on image to view a larger version of it.

We inherit two genes for every protein we make, one from our mother and one from our father. But we can only use one gene at a time. This means that the unused gene must be stopped from being copied into a message and subsequently translated into a protein. Such “silencing” of the gene is accomplished through either histone deacetylation or DNA methylation, two well known processes that result independently in a tight packaging of DNA that then cannot be translated into protein.

There is exciting proof now that it is these mechanisms that largely account for the physical differences in workers and queen honeybees who share the same set of genes. Phenyl butyrate, the magic substance in the royal jelly, is well known to inhibit histone deacetylation.  And it has recently been demonstrated that worker bees become queens if DNA methylation is prevented, even without the presence of royal jelly.

The implications of these findings have far-reaching consequences in a variety of disciplines, including the study of cancer and aging.

Cancer cells are marked by their ability to multiply continuously. They achieve this pseudo-immortality by silencing genes that tell the cell to die. These death-inducing genes are collectively referred to as tumor suppressor genes, or TSGs. And yes, TSGs are silenced by histone deacetylation and hypermethylation.

This means that agents that can cause inhibition of histone deacetylation, such as phenyl butyrate, and hypomethylating drugs, such as the cancer drugs Vidaza (azacitidine) and Dacogen (decitabine), should reactivate silenced TSGs and lead to the death of cancer cells.

Interestingly, when histone deacetylation and hypomethylating drugs were given to patients with a variety of cancers, both types of drugs produced the best responses in myelodysplastic syndromes (MDS).

MDS begins in a single stem cell of the bone marrow. The marrow is an organ in our bodies that makes blood cells. In fact, it makes approximately 500 billion blood cells every 24 hours. Surprisingly, these billions of cells are the daughters of just a few hundred stem cells.

In MDS, a single stem cell, now called the MDS stem cell, starts producing blood cells more rapidly than its normal counterparts. Before long, its daughters take over the entire marrow so that, in a short period of time, every cell in the blood or marrow of an MDS patient is descended from this abnormal cell, a state referred to as monoclonality.

But all is not normal with these MDS blood cells, since many of them are primed to die prematurely. Thus, even as the rate of cell birth in an MDS patient’s marrow is higher than normal, the blood counts begin to fall because of their excessive premature death. Red blood cells appear to be more commonly affected, and having low red blood cell counts (anemia) is the hallmark of MDS, with a smaller percentage of patients showing a decrease in white blood cells and platelets.

MDS can be divided into two types: low risk and high risk, referring to the risk of progressing to leukemia. A good half of all types of MDS patients respond to the hypomethylating drugs. These drugs improve the patients’ blood counts and can double their survival. A third of MDS patients, however, have some daughter cells that stop maturing but also develop mechanisms to ward off their premature death. These cells collect as immature blasts, and when their number makes up 20 percent of the marrow cells, we call the disease acute myeloid leukemia.

So, is it possible that MDS could be better treated with royal jelly from honeybees?

Research has also shown that the life expectancy of Americans depends on their ethnicity. American Indian males have the shortest life expectancy (55 years), while the longest is 92 years for South Asian women living in New Jersey! It turns out that the latter stick to their ethnic diet, which is rich in spices, especially turmeric. The active ingredient in turmeric is a substance called curcumin, which has been found to have anti-cancer properties.

I have used curcumin in low-risk MDS patients. A third of those treated with curcumin for at least six months have shown improvement in all three blood counts. Recently, it has been shown that curcumin acts as both a hypo­methyl­ating agent and as a histone deacetylase inhibitor.

What could be more interesting for immediate investigation than a substance that determines life spans in honeybees (royal jelly) and one which prolongs life spans in South Asian women (turmeric) and which is also useful for the treatment of MDS? Is turmeric the human royal jelly?

Dr. Azra Raza is Director of the MDS Center at Columbia University and a physician at New York-Presbyterian Hospital in New York City. Her primary area of research focuses on myelodysplastic syndromes and related conditions.  Dr. Raza writes a quarterly column for The MDS Beacon.

Upper Left: Photo of Dr. Azra Raza, Director of the MDS Center at Columbia University and a physician at New York-Presbyterian Hospital in New York City. Middle Left: Image from the National Institutes of Health; in the public domain.
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7 Comments »

  • Barb Morgan said:

    Dr. Raza, what is the turmeric daily dosage that you recommend? Should the dosage vary with low platelets or low RBC? Is there a preferred brand?
    Thanks.

  • Budh prakash goyal said:

    My hb level was falling since 2006. By year 2010 it had fallen to 10. General physician did not bother much till end of 2010,when serious investigations started. Lot many tests were conducted but no diagnosis was found. Finally I was advised to go through bone marrow biopsy in May 2011. Was it megaloblastic anemia or MDS was the confusion. So far all tests were conducted in india of which I am a resident.

    In July 2011 I landed in UK at Kings College with Dr Ghulam Mufti. After conducting blood tests & bone marrow biopsy MDS was confirmed. I was put on darbopoetein & GCSF injections. Because of calf muscle pains GCSF was discontinued. Not much improvement was seen in Hb except initially when it went up by 0.6gm but continued to fall thereafter. Currently my Hb level is 6.9/7 & have taken five units of blood since June 2012. Last blood transfusion was on 14th Jan and latest Hb is 6.9.

    I live in Delhi India & we regularly use turmeric in cooking. I read your article & was inspired to know that turmeric could be useful in helping low risk MDS patients. I have blast cells less than four percent & ringed sideroblast of 34 percent. no chromosomal abnormality. Can I get benefit by use of turmeric. What should be the dosage & how best to take. Should it be fresh or dry as used as condiment is ok. Your reply would be eagerly awaited.

    Regards & thanks

  • ZJ said:

    Dear Barb and Budh,

    You can find some information from the following link from Dr. Raza.

    http://www.umassmed.edu/hema_oncology/MDSInfo/curcuminandgingerol.aspx

  • ZJ said:

    ZJ,
    Am having trouble finding gingerol. Do you know what brand Dr. Raza is using for gingerol.

  • Mini Seth said:

    Dear Budh Prakash Goyal, I am from Delhi as well. My mother seems to be going through a similiar uncertainity phase as you may have gone through. It will be helpful if we can learn and get some advice based on your experience. Is there a way I can connect with you?

    Mini

  • Win Kryda said:

    Is it true that curcumin affects clotting factor? And if so isn’t there concern with low platelets? Thanks. Win RN

  • Zygfryd Ostrowski said:

    I have myelodysplastic syndrome with refractory anemia with ringed sideroblast and I am taking Pro chemia – natural tablets, but they do not work with me. Now I am on blood transfusion every two weeks. My hemoglobin is 6.5 and it starts to giving my heart problem. Does someone knows about Bees treatment?
    Sincerely
    Zygfryd