Understanding the Disease

Advanced KIT+ GIST and Ph+ CML

Get information about the conditions that GLEEVEC is approved to treat. Please select either KIT+ GIST or Ph+ CML to learn more.

Get information about the conditions that GLEEVEC is approved to treat. Please select either KIT+ GIST or Ph+ CML to learn more.

Get information about the conditions that GLEEVEC is approved to treat. Please select either KIT+ GIST or Ph+ CML to learn more.

What Are GIST and KIT+ GIST?

KIT is a protein that controls reproduction of cells. It is believed that increased KIT activity leads to cancer cells growing out of control, eventually forming a tumor. In this case, the tumor is called a gastrointestinal stromal tumor, or GIST. GIST is a rare disease that occurs mostly in the stomach. However, GIST may develop anywhere along the digestive tract, from the esophagus all the way down to the rectum. In advanced GIST, the tumor can grow bigger at its original site, or it can spread to other parts of the body, such as the liver. When KIT+ GIST can’t be removed by surgery (called “inoperable”), or it has spread (considered “metastatic”), it is often called “advanced KIT+ GIST.”

Why Are Some KIT+ GISTs "Inoperable"?

The goal of surgery is to remove the tumor intact. A KIT+ GIST tumor may be considered inoperable if it is large or if removal might cause the tumor to rupture. Tumor rupture could cause KIT+ GIST to spread. If complete removal isn’t possible, your surgeon may decide not to operate.

How Is Advanced KIT+ GIST Managed?

GLEEVEC® (imatinib mesylate) tablets is the only first-line medication approved by the FDA for the treatment of advanced KIT+ GIST. GLEEVEC is not a cure.

If GLEEVEC 400 mg does not stop tumor growth, your doctor may increase your dose to 800 mg (400 mg taken twice daily), assuming you are not experiencing serious side effects. Talk to your oncologist and/or health care professional about any side effects you are experiencing while taking GLEEVEC. It's important to stay on GLEEVEC for as long as your doctor prescribes it.

What Is Ph+ CML?

Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) is a type of cancer of the bone marrow and blood. In people with Ph+ CML, the bone marrow (the soft tissue inside bones where blood cells are made) produces too many white blood cells, and these cells are often immature or damaged. About 8430 patients in the United States were diagnosed with CML in 2018, and the median age of diagnosis is 67.

A Closer Look at Ph+ CML

"Ph" is an abbreviation for “Philadelphia chromosome,” the name given to the abnormal chromosome that can lead to the overproduction of white blood cells. The positive sign (+) means that your laboratory tests show your bone marrow and white blood cells contain the abnormal Philadelphia chromosome. "Chronic" means that it progresses slowly. "Myeloid" refers to the type of white blood cells that are affected. "Leukemia" tells you it is a cancer of the bone marrow and white blood cells.

So when your doctor says you have Ph+ CML, it means that your bone marrow cells have an abnormal chromosome, and your body is producing too many white blood cells. In addition to crowding out normal, healthy cells, these white blood cells often do not function normally.

How Does Ph+ CML Happen?

The soft tissue inside our bones, called the bone marrow, produces a type of cell called a stem cell. As stem cells mature, they can turn into platelets, red blood cells, or white blood cells. Ph+ CML happens because of changes in the genetic material of these stem cells.

Chromosomes are the parts of our cells that carry our DNA and genes—the things that give us our physical traits, such as blue eyes or brown hair, and that tell our body how to handle all the functions of life, including the process of making blood cells. Humans have 23 pairs of chromosomes. Ph+ CML happens when some genetic material from one chromosome (chromosome 9) switches position with some genetic material from another chromosome (chromosome 22).

The new genetic material on chromosome 22 is called BCR-ABL and leads to abnormalities in your body's process for making blood cells. When chromosome 22 has this abnormal BCR-ABL gene, scientists call it the Philadelphia chromosome. People with Ph+ CML have the BCR-ABL gene in their stem cells and white blood cells. The BCR-ABL gene produces a protein called Bcr-Abl. Scientists distinguish between the name of the gene and protein by how they are written.

The Bcr-Abl protein causes your bone marrow to produce more and more white blood cells, and these white blood cells are often damaged. It acts like a switch that keeps your white blood cell production in the "on" position. Normally, your body would stop producing white blood cells that weren't needed and damaged blood cells would die off, but the Bcr-Abl protein interferes with these processes. Instead, your bone marrow keeps making damaged white blood cells that, over time, crowd out healthy red blood cells and platelets.

Scientists do not know exactly why the genetic material switches between the 2 chromosomes and continue to search for causes of Ph+ CML. Although Ph+ CML involves genetic material, be assured that it is not inherited. The abnormal gene is not passed down from parent to child.

Signs and Symptoms of Ph+ CML

Some common symptoms of Ph+ CML are:

  • Feeling very tired all the time
  • Bruising easily or bleeding that takes longer to stop than normal
  • Unexplained weight loss
  • Pain in the bones and joints

Many people are diagnosed in the early stage of Ph+ CML and do not have any obvious signs and symptoms. Often, Ph+ CML is discovered during a routine blood test when results show the person has an elevated white blood cell count.