Leukemia and other diseases of the blood and bone marrow may affect red blood cells, white blood cells and platelets.
Normally, the bone marrow makes blood stem cells, also called hematopoietic stem cells, immature cells that develop into mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.
The myeloid stem cell develops into one of three types of mature blood cells:
Red blood cells that carry oxygen and other materials to all tissues of the body
Granulocytes (white blood cells comprising three subtypes – eosinophils, neutrophils and basophils) that fight infection and disease
Platelets that help prevent bleeding by causing blood clots to form
The lymphoid stem cell develops into a lymphoblast cell and then into one of three types of lymphocytes (white blood cells):
B lymphocytes that make antibodies to help fight infection
T lymphocytes that help B lymphocytes make the antibodies that help fight infection
Natural killer (NK) cells that attack cancer cells and viruses.
Leukemia is a cancer of the blood and bone marrow in which abnormal, immature blood cells (lymphoid or myeloid) are produced in great quantities. These cells do not perform their normal functions, and are known as leukemic cells. The leukemic cells are malignant (cancerous) and crowd out normal blood cells, preventing them from fighting infection and causing serious problems which may be fatal if untreated.
Acute lymphoblastic leukemia (ALL)
Acute lymphoblastic leukemia (ALL), one of two major lymphoid leukemias, is the most common type of cancer in children, though it may also occur in adults. It is also referred to as acute lymphocytic or acute lymphoid leukemia.
In ALL, too many stem cells develop into lymphoblasts, which would ordinarily develop into mature lymphocytes. However, in ALL, these blasts do not ever fully develop. These abnormal cells are known as leukemic cells, and are not able to fight infection. As the number of leukemic cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells and platelets. This may cause infection, anemia and easy bleeding. The cancerous leukemic cells can also spread to the central nervous system (brain and spinal cord). ALL is an aggressive, acute leukemia, and progresses rapidly without treatment. However, modern combination chemotherapy protocols have made childhood ALL highly treatable, with remission achieved in a majority of patients.
Subgroups of Childhood ALL
Four of the subgroups of childhood ALL are based on the type of blood cell that is affected, whether there are certain changes in the chromosomes, and age at diagnosis:
T cell ALL (most ALL is B cell in origin)
Philadelphia chromosome-positive ALL
ALL diagnosed in an infant
ALL diagnosed in children age 10 and older and adolescents (teenagers)
These subgroups are treated differently from other types of ALL.
Chronic lymphocytic leukemia (CLL)
Chronic lymphocytic leukemia (CLL) represents the other major form of lymphoid leukemia. CLL is the second most common type of leukemia in adults. It often occurs during or after middle age; it rarely occurs in children. As in ALL, too many blood stem cells develop into abnormal lymphocytes (leukemic cells) and do not become healthy white blood cells. These immature leukemic lymphocytes are not able to fight infection. Also, as the number of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells and platelets. This may result in infection, anemia and easy bleeding.
Unlike ALL, however, CLL usually progresses slowly, and often requires no treatment initially. This is known as an “indolent” or “smoldering” variety of CLL. However, depending on the individual patient’s genetics, CLL may progress rapidly and have a poorer prognosis. In addition to a complete blood work-up, cytogenetic testing using the fluorescence in situ hybridization technique is recommended to determine the best course of treatment. Most CLL cases are known as B-CLL, meaning that the cancer derives from B lymphocytes. Much rarer is T-CLL, in which the leukemic cells are T cells rather than B cells.
Hairy cell leukemia
Hairy cell leukemia is a rare type of lymphoid leukemia often classified as a subtype of CLL, and is usually slow-growing. However, there is a variant (called HCL-V) which behaves more aggressively. The disease is called hairy cell leukemia because the leukemia cells look "hairy" when viewed under a microscope.
In hairy cell leukemia, as in other lymphoid leukemias, too many blood stem cells develop into lymphocytes. These lymphocytes are abnormal and do not become healthy white blood cells. They may also be called leukemic cells. The leukemic cells can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells and platelets. This may cause infection, anemia and easy bleeding. Some of the leukemia cells may collect in the spleen and cause it to swell.
Adult T cell leukemia/lymphoma (ATLL)
Adult T cell leukemia/lymphoma (ATLL) is a rare type of lymphoid leukemia in which T cells are the abnormal leukemic cells, rather than the B cells found in most lymphoid leukemias. ATLL is thought to be almost exclusively caused by infection with a retrovirus called human T cell lymphotropic virus (HTLV-1). ATLL may exist in both acute and chronic forms. The acute form progresses rapidly and has a poorer prognosis. It also has a smoldering form, in which the disease is more stable than the chronic form, and a lymphoma form, where the lymph nodes are involved to a greater extent than the blood.
Acute myeloid leukemia (AML)
Acute myeloid leukemia (AML) is one of two major types of myeloid leukemia. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia or acute nonlymphocytic leukemia. It is the second most common type of leukemia in adults.
In AML, the myeloid stem cells usually develop into a type of immature white blood cell called myeloblasts (or myeloid blasts). The myeloblasts in AML are abnormal and do not become healthy white blood cells. These abnormal blasts are leukemic cells. Sometimes in AML, too many stem cells develop into abnormal red blood cells or platelets. These abnormal red blood cells or platelets are also called leukemia cells or blasts. The leukemia cells can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells and platelets. When this happens, infection, anemia or easy bleeding may occur.
The leukemia cells can spread outside the blood to other parts of the body, including the central nervous system (brain and spinal cord), skin (known as leukemia cutis) and gums. Sometimes leukemia cells form a solid tumor called a granulocytic sarcoma or chloroma (so-called because of its blue-green color). While these tumors may occur almost anywhere, the most common sites are the skin and gums.
AML is an aggressive disease, and commensurately aggressive treatment is required. This may include combination chemotherapy, radiation and/or bone marrow or stem cell transplantation.
Subtypes of Acute Myeloid Leukemia
There are subtypes of acute myeloid leukemia (AML) based on the type of blood cell that is affected as well as specific genetic characteristics. Genetic mutations called translocations, in which a section of genes on one chromosome is literally swapped with a section of genes on a completely different chromosome, are quite prevalent in AML.
Acute promyelocytic leukemia (APL)
Acute promyelocytic leukemia (APL), also called acute progranulocytic leukemia, results from the overaccumulation of immature myelocytes called progranulocytes. As with other forms of AML, a genetic translocation is thought to be the cause, with a section of chromosome containing a gene called RARA being translocated in this case. The RARA gene encodes for a receptor for retinoic acid, a derivative of vitamin A. This knowledge has led to APL being treated with all-trans-retinoic acid, to which it is uniquely sensitive and highly therapeutically responsive.
Juvenile myelomonocytic leukemia (JMML)
Juvenile myelomonocytic leukemia (JMML) is a rare childhood cancer that occurs more often in children younger than two years. In JMML, too many bone marrow stem cells develop into two types of white blood cells called myelocytes and monocytes. Some of these bone marrow stem cells never become mature white blood cells. These immature cells, called blasts, are unable to do their usual work. Over time, the myelocytes, monocytes, and blasts crowd out the red blood cells and platelets in the bone marrow. When this happens, infection, anemia or easy bleeding may occur.
Transient myeloproliferative disorder (TMD)
Transient myeloproliferative disorder (TMD) is a disorder of the bone marrow that can develop in newborns who have Down's syndrome. This disorder usually goes away on its own within the first three weeks of life. Infants who have Down's syndrome and TMD have an increased chance of developing AML before three years of age.
In myelodysplastic syndromes, the bone marrow makes too few red blood cells, white blood cells and platelets. These blood cells may not mature and enter the blood. The treatment for myelodysplastic syndromes depends on how much lower than normal the number of red blood cells, white blood cells or platelets is. Myelodysplastic syndromes may progress to AML.
Down's syndrome and AML
Children with Down's syndrome and certain other genetic abnormalities such as neurofibromatosis type 1 have a much greater chance of developing AML, JMML, TMD and myelodysplastic syndrome. Most AML in Down's syndrome patients originates as some type of myelodysplasia. AML patients with Down's syndrome have two important characteristics: 1) they are significantly more responsive to chemotherapy than non-Down AML patients, and 2) their leukemic cells exhibit much greater sensitivity to a chemotherapy drug called cytosine arabinoside.
About Chronic Myelogenous Leukemia (CML)
In chronic myelogenous leukemia (CML), the other major form of myeloid leukemia, too many bone marrow stem cells develop into a type of white blood cell called granulocytes. Some of these bone marrow stem cells never become mature white blood cells. These immature cells are called blasts. Over time, the granulocytes and blasts crowd out the red blood cells and platelets in the bone marrow. CML is rare in children. The hallmark of CML is the presence of what is known as the Philadelphia chromosome, an abnormal chromosome containing an oncogene (cancer-causing gene). The course of this disease is much slower than with AML (hence the description “chronic.”) However, patients with advanced CML may experience what is known as a “blast crisis,” which resembles AML clinically, where there is a large and sudden proliferation of blasts. CML is also particularly responsive to a relatively new drug therapy called Gleevec.