v4n1 - Megakaryocytes & Platelet Production

CURE, Spring 2005, Volume 4, Issue 1

Megakaryocytes are the parent cells that make platelets—sticky bodies that circulate in the bloodstream and help the blood to clot when you get cut. They are also the culprits that contribute to clot formation inside arteries and blood vessels, which can lead to strokes or heart attacks.

A single megakaryocyte can make between 1,000 and 3,000 platelets during its life span. Platelets are pinched off or shed from the parental megakaryocte and are made up of pieces of the megakaryocyte’s membrane. They contain granules with clotting factors and other proteins inside. Normally, there are about 150,000 to 400,000 platelets in every microliter of blood, and while this number can vary between people, it usually stays the same in a particular person throughout a lifetime, unless platelet production is disturbed. If the body suddenly has a higher need for platelets, the megakaryocytes in the bone marrow respond by dividing, increasing in size and producing more platelets.

Many types of chemotherapy can kill megakaryocytes, and it takes them time to regenerate. This can lead to a condition called thrombocytopenia, and, if left uncorrected, can lead to problems with bleeding and clotting. Usually, though not always, the numbers of megakaryocytes will eventually rebound after chemotherapy is stopped.

Not all forms of chemotherapy-related thrombocytopenia occur because the megakaryocytes have died. Velcade, one of the newer targeted agents, causes a transient drop in platelet counts without a corresponding drop in the number of megakaryocytes. This is because, although the megakaryocyte itself is left undisturbed, Velcade inhibits the platelets from budding off from the megakaryocyte. This process is reversed during the time between doses or once treatment has been completed.

Megakaryocytes need a protein called thrombopoietin (also known as megakaryocyte growth and development factor) in order to grow and

survive. This growth factor sends a signal to the megakaryocyte to divide and mature. For this reason, researchers are experimenting with synthetic forms of thrombopoietin to determine if this protein could help prevent chemotherapy-induced thrombocytopenia.

Studies in both animals and humans suggest synthetic forms can stimulate megakaryocyte development and platelet production, without notable side effects. In the future, this approach may be useful in protecting cancer patients from one of the more serious side effects of chemotherapy