Types of Leukemia

Leukemia is classified by how quickly it progresses. Acute leukemia is fast-growing and can overrun the body within a few weeks or months. By contrast, chronic leukemia is slow-growing and progressively worsens over years.

Acute versus Chronic Leukemia

The blood-forming (hematopoietic) cells of acute leukemia remain in an immature state, so they reproduce and accumulate very rapidly. Therefore, acute leukemia needs to be treated immediately, otherwise the disease may be fatal within a few months. Fortunately, some subtypes of acute leukemia respond very well to available therapies and they are curable. Children often develop acute forms of leukemia, which are managed differently from leukemia in adults.

In chronic leukemia, the blood-forming cells eventually mature, or differentiate, but they are not "normal." They remain in the bloodstream much longer than normal white blood cells, and they are unable to combat infection well.

Myelogenous versus Lymphocytic Leukemia

Leukemia also is classified according to the type of white blood cell that is multiplying–that is, lymphocytes (immune system cells), granulocytes (bacteria-destroying cells), or monocytes (macrophage-forming cells). If the abnormal white blood cells are primarily granulocytes or monocytes, the leukemia is categorized as myelogenous, or myeloid, leukemia. On the other hand, if the abnormal blood cells arise from bone marrow lymphocytes, the cancer is called lymphocytic leukemia.

Other cancers, known as lymphomas, develop from lymphocytes within the lymph nodes, spleen, and other organs. Such cancers do not originate in the bone marrow and have a biological behavior that is different from lymphocytic leukemia.

There are over a dozen different types of leukemia, but four types occur most frequently. These classifications are based upon whether the leukemia is acute versus chronic and myelogenous versus lymphocytic, that is:

  • Acute Myelogenous (granulocytic) Leukemia (AML)
  • Chronic Myelogenous (granulocytic) Leukemia (CML)
  • Acute Lymphocytic (lymphoblastic) Leukemia (ALL)
  • Chronic Lymphocytic Leukemia (CLL)

Acute Myelogenous Leukemia (AML)

Acute myelogenous leukemia (AML)—also known as acute nonlymphocytic leukemia (ANLL)—is the most common form of adult leukemia. Most patients are of retirement age (average age at diagnosis is 65 years), and more men are affected than women. Fortunately, because of recent advances in treatment, AML can be kept in remission (lessening of the disease) in approximately 60 to 70 percent of adults who undergo appropriate therapy. Initial response rates are approximately 65-75 percent, but the overall cure rates are more on the order of 40-50 percent.

AML begins with abnormalities in the bone marrow blast cells that develop to form granulocytes, the white blood cells that contain small particles, or granules. The AML blasts do not mature, and they become too numerous in the blood and bone marrow. As the cells build up, they hamper the body's ability to fight infection and prevent bleeding. Therefore, it is necessary to treat this disease within a short time after making a diagnosis. AML, particularly in the monocytic M5 form, may spread to the gums and cause them to swell, bleed, and become painful. AML also may metastasize (spread) to the skin, causing small colored spots that mimic a rash.

Acute leukemia, such as AML, is categorized according to a system known as French-American-British (FAB) classification. FAB divides AML into eight subtypes:

  • undifferentiated AML (M0)—In this form of leukemia, the bone marrow cells show no significant signs of differentiation (maturation to obtain distinguishing cell characteristics).
  • myeloblastic leukemia (M1; with/without minimal cell maturation)—The bone marrow cells show some signs of granulocytic differentiation.
  • myeloblastic leukemia (M2; with cell maturation)—The maturation of bone marrow cells is at or beyond the promyelocyte (early granulocyte) stage; varying amounts of maturing granulocytes may be seen. This subtype often is associated with a specific genetic change involving translocation of chromosomes 8 and 21.
  • promyelocytic leukemia (M3 or M3 variant [M3V])—Most cells are abnormal early granulocytes that are between myeloblasts and myelocytes in their stage of development and contain many small particles. The cell nucleus may vary in size and shape. Bleeding and blood clotting problems, such as disseminated intravascular coagulation (DIC), are commonly seen with this form of leukemia. Good responses are observed after treatment with retinoids, which are drugs chemically related to vitamin A.
  • myelomonocytic leukemia (M4 or M4 variant with eosinophilia [M4E])—The bone marrow and circulating blood have variable amounts of differentiated granulocytes and monocytes. The proportion of monocytes and promonocytes (early monocyte form) in the bone marrow is greater than 20 percent of all nucleated (nucleus-containing) cells. The M4E variant also contains a number of abnormal eosinophils (granular leukocyte with a two-lobed nucleus) in the bone marrow.
  • monocytic leukemia (M5)—There are two forms of this subtype. The first form is characterized by poorly differentiated monoblasts (immature monocytes) with lacy-appearing genetic material. The second, differentiated form is characterized by a large population of monoblasts, promonocytes, and monocytes. The proportion of monocytes in the bloodstream may be higher than that in the bone marrow. M5 leukemia may infiltrate the skin and gums, and it has a worse prognosis than other subtypes.
  • erythroleukemia (M6)—This form of leukemia is characterized by abnormal red blood cell-forming cells, which make up over half of the nucleated cells in the bone marrow.
  • megakaryoblastic leukemia (M7)—The blast cells in this form of leukemia look like immature megakaryocytes (giant cells of the bone marrow) or lymphoblasts (lymphocyte-forming cells). M7 leukemia may be distinguished by extensive fibrous tissue deposits (fibrosis) in the bone marrow.

In addition, patients sometimes develop isolated tumors of the myeloblasts (early granulocytes). An example of this is isolated granulocytic sarcoma, or chloroma—a malignant tumor of the connective tissue. Individuals with chloroma frequently develop AML, so they usually are treated with an aggressive, AML-specific chemotherapy program.

Chronic Myelogenous Leukemia (CML)

Chronic myelogenous leukemia (CML) is known as a myeloproliferative disorder—that is, it is a disease in which bone marrow cells proliferate (multiply) outside of the bone marrow tissue.

CML is easy to diagnose, since it has a genetic peculiarity, or marker, that is readily identifiable under a microscope. About 95% of CML patients have a genetic translocation between chromosomes 9 and 22 in their leukemic cells. This abnormality, which is known as the Philadelphia chromosome (Ph1), is named after the city in which it was discovered. The Philadelphia chromosome causes uncontrolled reproduction and proliferation of all types of white blood cells and platelets (blood clotting factors). Sadly, CML is not yet curable by standard methods of chemotherapy or immunotherapy.

CML tends to occur in middle- and retirement-aged people (the median age is 67 years). It occasionally affects people in their 20s, but it is rare in the very young; only 2 to 3 percent of childhood leukemias are CML. Early disease often is without symptoms (asymptomatic) and is discovered accidentally. Individuals with more advanced cases of CML may appear sickly and experience fevers, easy bruising, and bone pain. Laboratory and physical findings include enlarged spleen (splenomegaly), a high white blood cell count, and absent or low amounts of the white blood cell enzyme alkaline phosphatase.

Like other forms of leukemia, CML is not "staged." Rather, this unstable disease is categorized according to the three phases of its development: chronic, accelerated, and blast.

  • Chronic phase—Patients in this initial phase have fewer than 5 percent blast cells and promyelocytes (immature granulocytes) in their blood and bone marrow. This phase is marked by increasing overproduction of granulocytes. Individuals generally experience only mild symptoms, and they respond well to conventional treatment.
  • Accelerated phase—Patients in this progressive phase have more than 5 percent, but fewer than 30 percent blast cells. Their leukemic cells exhibit more chromosomal abnormalities besides the Philadelphia chromosome, and so more abnormal cells are produced. Noticeable symptoms such as fever, poor appetite, weight loss occur, and patients may not respond as well to therapy.
  • Blast phase (acute phase, blast crisis)—Patients in this final phase have more than 30 percent blast cells in their blood and bone marrow samples. The blast cells frequently invade other tissues and organs outside of the bone marrow. During this phase, the disease transforms into an aggressive, acute leukemia (70 percent acute myelogenous leukemia, 30 percent acute lymphocytic leukemia). If untreated, CML is fatal in roughly 20 percent of all patients each year.

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 13 Aug 1999

Last Modified: 24 Sep 2015