A Look at Hematopoiesis

Hematopoiesis (pronounced heem-at-oh-po-EE-sus) is the process by which all of your blood cells are formed, develop and mature into their final adult types.

The term refers to the pathways or tracks of blood cell development, beginning with what’s known as a hematopoietic stem cell (HSC), going through a series of steps to arrive at the final product—a mature blood cell, whether it’s a red blood cell, a white blood cell such as a lymphocyte, or some other type of blood cell. Other terms for this process of blood cell formation include hematogenesis, hemogenesis, and hemopoiesis.

The sites of blood cell production depend on whether you are talking about a baby still in its mother’s womb, or afterward during infancy and throughout adulthood. That is, in utero, a developing child uses a variety of different sites in the body for hematopoiesis, including the liver, spleen, thymus, lymph nodes, as well as bone marrow. After birth, the main site of hematopoiesis is in the bone marrow.

Extramedullary hematopoiesis is the formation of blood cells at sites other than the bone marrow. And while extramedullary hematopoiesis is the norm for a baby in the womb, once a person is born, it is generally a sign of disease or an indication that the bone marrow is unable to produce enough healthy red blood cells to meet the demand.

What Is Hematopoietic?

You might come across the word hematopoiesis, or the adjective hematopoietic, in a number of different scenarios:

• Hematopoietic stem cell transplantation, also called bone marrow transplant or stem cell transplant, involves taking donated stem cells and giving them to a recipient, so that the recipient can make his or her own new red blood cells, white blood cells, and platelets that help blood to clot.
• Hematopoietic malignancy refers to cancer of the blood-forming cells. Hematopoietic malignancies include leukemia, lymphoma, and myeloma.
• Hematopoietic neoplasm covers a wide range of blood disorders, some of which are chronic conditions that you live with, and others are more apt to progress with serious complications and decreased survival.
• Hematopoietic cell lineage or cell line refers to the several tracks, or branches in the blood cell "family tree," by which a progenitor cell develops into an adult/mature blood cell.

Overview

Circulating blood contains a mix of cells, cell products, and fluids. Our bodies produce blood cells continuously from the time we are in the womb up to old age. Millions of blood cells are replaced each day as they live out their lifespans. Different types of cells have different lifespans, and in healthy adults, red blood cells normally live about 100 to 120 days before they need to be replaced.

There are more than 10 different kinds of blood cells, each performing its own set of tasks. Though red and white blood cells may end up in different places in the body, production starts in the bone marrow.

In the Bone Marrow

Within the hollows of certain bones, the marrow tissue exists, including hematopoietic stem cells (also called pluripotent hematopoietic stem cells) that give rise to all of the different types of blood cells. Some of these stem cells remain "uncommitted" so that they can continue to reproduce cells of whatever type is needed, sort of like a queen bee laying eggs, but other stem cells start the process of committing, to become "progenitors" or "precursors" of distinctly different cell lines. Cell lines/lineages can be thought of as different branches of the blood cell family tree.

Blood-forming cells make for two different sides of the family tree:

• The lymphoid side is easier to remember because it gives rise to the white blood cells known as lymphocytes. Lymphocytes can be further classified as T cells, B cells, and natural killer cells.
• The myeloid side of the family is more of a hodgepodge. You have your red blood cells, which are also called erythrocytes, as well as your blood platelets, which are basically little pieces of huge cells called megakaryocytes. But then, in addition to your red blood cells and platelets, you also have all of the white blood cells that come from myeloid progenitors: neutrophils, monocytes, eosinophils, and basophils are all white blood cells that come from the myeloid progenitors.
• Under normal circumstances, a good part of the early growth and maturation of many of these cell types occurs within the bone marrow; T-cells develop in the bone marrow but move to the thymus to mature.

In the Blood, Fluids, and Tissues

Once grown and mature, red blood cells stay in the blood. White blood cells may also be found in the bloodstream, but they may be more prevalent at other sites. For instance, lymphocytes are far more common and numerous in the lymphatic system than in the blood.

• White blood cells (leukocytes): These include lymphocytes, monocytes and polymorphonuclear white cells that provide our bodies with protection from infection. White blood cells are key components of our immune system that help destroy invaders using a variety of tactics, including the production of antibodies that stick to the invaders. Problems with white blood cells can lead to infection.
• Red blood cells (erythrocytes): These cells contain the hemoglobin that gives your blood its red color and carries oxygen to the cells and tissues in your body. Deficiency of red blood cells can lead to anemia, with symptoms such as fatigue, weakness, and intolerance to exercise.
• Platelets: Megakaryocytes in the bone marrow are enormous cells in comparison to the other blood cells, and they produce little packages of cellular material (platelets) that help control bleeding after an injury. Platelet deficiencies can lead to easy bruising and trouble with bleeding.

From Bone Marrow to Bloodstream

If the HSC commits to producing mature blood cells, it will undergo several cell divisions before becoming that cell. Every time the cell divides, it takes on more of the characteristics of the adult cell it will become. In other words, it becomes more differentiated or specialized.

Stimulating the body to produce more new blood cells—a sort of artificial hematopoiesis–can be helpful in certain situations. For instance, sometimes the bone marrow is stimulated in advance of a planned cancer therapy when profound suppression of the blood-forming cells in the marrow is expected.

When Hematopoietic Cells Go Astray

Like any cell, the HSCs can undergo a mutation that leads to dysfunctional or malignant cells being produced rather than healthy cells. Depending on what stage of differentiation the cell is in when it makes this transformation, it gives rise to different types of disorders: myeloproliferative disorders, leukemias, lymphomas, and myelomas.

An abnormal younger cell type may be referred to as a ‘blast.’ Blasts in patients with leukemia can suggest the cancerous transformation occurred in a blood-forming cell that was at an earlier stage of development. If the predominant cells in leukemia or lymphoma are more mature types, this indicates the cancerous transformation happened to a more mature cell or a cell that was closer to the final adult stage.

In lymphoma, there can be different lymphomas that reflect all different stages of lymphocyte development, including the developmental paths for B-cells and T-cells; thus, there are B-cell lymphomas, T-cell lymphomas, and even natural killer T-cell lymphomas.

Hematopoietic Cell Transplantation - Bone Marrow Transplants

The treatment of leukemia, lymphoma and other blood cancers may involve a transplant of hematopoietic stem cells. These can be your own cells, harvested from your bone marrow (autologous), or from a donor (allogeneic). Techniques used to obtain healthy blood-forming cells from the donor vary, but the transplant itself is a simple transfusion as the hematopoietic stem cells migrate from the blood into the bone marrow.

Extramedullary Hematopoiesis

This is the term used for blood cell production that occurs outside of the bone marrow. It can be seen in chronic anemia, with the production of blood cells in the liver, spleen and sometimes in the lymph nodes. In other scenarios, there may be malignant hematopoietic cells located in areas outside of the bone marrow.