Chronic Myelogenous Leukemia

Chronic Myelogenous Leukemia Overview

Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the bone marrow — the spongy tissue inside bones where blood cells are made. CML causes an increased number of white blood cells in the blood.

The term “chronic” in chronic myelogenous leukemia indicates that this cancer tends to progress more slowly than acute forms of leukemia. The term “myelogenous” in chronic myelogenous leukemia refers to the type of cells affected by this cancer.

Chronic myelogenous leukemia can also be called chronic myeloid leukemia and chronic granulocytic leukemia. It typically affects older adults and rarely occurs in children, though it can occur at any age.

Advances in treatment have contributed to a greatly improved prognosis for people with chronic myelogenous leukemia. Most people will achieve remission and live for many years after diagnosis.

Chronic Myelogenous Leukemia Symptoms

Chronic myelogenous leukemia often doesn’t cause signs and symptoms. It might be detected during a blood test.

When they occur, signs and symptoms may include:

  • Bone pain
  • Easy bleeding
  • Feeling full after eating a small amount of food
  • Feeling run-down or tired
  • Fever
  • Weight loss without trying
  • Loss of appetite
  • Pain or fullness below the ribs on the left side
  • Excessive sweating during sleep (night sweats)

Chronic Myelogenous Leukemia Causes

Chronic myelogenous leukemia occurs when something goes awry in the genes of your bone marrow cells. It’s not clear what initially sets off this process, but doctors have discovered how it progresses into chronic myelogenous leukemia.

An abnormal chromosome develops

Human cells normally contain 23 pairs of chromosomes. These chromosomes hold the DNA that contains the instructions (genes) that control the cells in your body. In people with chronic myelogenous leukemia, the chromosomes in the blood cells swap sections with each other. A section of chromosome 9 switches places with a section of chromosome 22, creating an extra-short chromosome 22 and an extra-long chromosome 9.

The extra-short chromosome 22 is called the Philadelphia chromosome, named for the city where it was discovered. The Philadelphia chromosome is present in the blood cells of 90 percent of people with chronic myelogenous leukemia.

The abnormal chromosome creates a new gene

The Philadelphia chromosome creates a new gene. Genes from chromosome 9 combine with genes from chromosome 22 to create a new gene called BCR-ABL. The BCR-ABL gene contains instructions that tell the abnormal blood cell to produce too much of a protein called tyrosine kinase. Tyrosine kinase promotes cancer by allowing certain blood cells to grow out of control.

The new gene allows too many diseased blood cells

Your blood cells originate in the bone marrow, a spongy material inside your bones. When your bone marrow functions normally, it produces immature cells (blood stem cells) in a controlled way. These cells then mature and specialize into the various types of blood cells that circulate in your body — red cells, white cells and platelets.

In chronic myelogenous leukemia, this process doesn’t work properly. The tyrosine kinase caused by the BCR-ABL gene allows too many white blood cells to grow. Most or all of these cells contain the abnormal Philadelphia chromosome. The diseased white blood cells don’t grow and die like normal cells. The diseased white blood cells build up in huge numbers, crowding out healthy blood cells and damaging the bone marrow.

Risk factors

Factors that increase the risk of chronic myelogenous leukemia:

  • Older age
  • Being male
  • Radiation exposure, such as radiation therapy for certain types of cancer

Chronic Myelogenous Leukemia Diagnostics

Tests and procedures used to diagnose chronic myelogenous leukemia include:

  • Physical exam. Your doctor will examine you and check such vital signs as pulse and blood pressure. He or she will also feel your lymph nodes, spleen and abdomen to determine whether they are enlarged.
  • Blood tests. A complete blood count may reveal abnormalities in your blood cells, such as a very high number of white blood cells. Blood chemistry tests to measure organ function may also reveal abnormalities that can help your doctor make a diagnosis.
  • Bone marrow tests. Bone marrow biopsy and bone marrow aspiration are used to collect bone marrow samples for laboratory testing. These tests involve collecting bone marrow from your hipbone.
  • Tests to look for the Philadelphia chromosome. Specialized tests, such as fluorescence in situ hybridization (FISH) analysis and the polymerase chain reaction (PCR) test, analyze blood or bone marrow samples for the presence of the Philadelphia chromosome or the BCR-ABL gene.

Chronic Myelogenous Leukemia Treatment

The goal of chronic myelogenous leukemia treatment is to eliminate the blood cells that contain the abnormal BCR-ABL gene that causes the overabundance of diseased blood cells. For most people, treatment begins with targeted drugs that may help achieve a long-term remission of the disease.

Targeted drug therapy

Targeted drugs are designed to attack cancer by focusing on a specific aspect of cancer cells that allows them to grow and multiply. In chronic myelogenous leukemia, the target of these drugs is the protein produced by the BCR-ABL gene — tyrosine kinase.

Targeted drugs that block the action of tyrosine kinase include:

  • Imatinib (Gleevec)
  • Dasatinib (Sprycel)
  • Nilotinib (Tasigna)
  • Bosutinib (Bosulif)
  • Ponatinib (Iclusig)

Targeted drugs are the initial treatment for people diagnosed with chronic myelogenous leukemia. 

Blood tests to detect the presence of the BCR-ABL gene are used to monitor the effectiveness of targeted drug therapy. If the disease doesn’t respond or becomes resistant to targeted therapy, doctors may consider other targeted drugs, such as omacetaxine (Synribo), or other treatments.

Doctors haven’t determined a safe point at which people with chronic myelogenous leukemia can stop taking targeted drugs. For this reason, most people continue to take targeted drugs even when blood tests show remission of the disease.

Bone marrow transplant

A bone marrow transplant, also called a stem cell transplant, offers the only chance for a definitive cure for chronic myelogenous leukemia. However, it’s usually reserved for people who haven’t been helped by other treatments because bone marrow transplants have risks and carry a high rate of serious complications.

During a bone marrow transplant, high doses of chemotherapy drugs are used to kill the blood-forming cells in your bone marrow. Then blood stem cells from a donor are infused into your bloodstream. The new cells form new, healthy blood cells to replace the diseased cells.

Chemotherapy

Chemotherapy is a drug treatment that kills fast-growing cells in the body, including leukemia cells. Chemotherapy drugs are sometimes combined with targeted drug therapy to treat aggressive chronic myelogenous leukemia. Side effects of chemotherapy drugs depend on what drugs you take.