Philadelphia chromosome positive chronic myeloid leukemia is a common form of chronic myeloid leukemia (CML), that occurs when specific chromosomes swap positions.
This causes an abnormality in the chromosomes, creating the Philadelphia chromosome, which then sends different growing instructions for the white blood cells in the person’s bone marrow.
Understanding the Philadelphia chromosome and its role in CML helps doctors find potential treatments for people with the disease.
Below, we examine the basics of the Philadelphia chromosome along with symptoms, causes, treatment, and prognosis for this form of CML.
Chronic myeloid leukemia (CML) is a rare type of leukemia affecting the bone marrow at the center of the person’s bones. Doctors consider CML a chronic disease, as it tends to progress more slowly than other forms of leukemia.
The National Organization for Rare Disorders notes that chronic myeloid leukemia makes up about 20% of all cases of adult leukemia. The Philadelphia chromosome occurs in 90% of people with CML.
The Philadelphia chromosome occurs with changes in some chromosomes in the body. Humans have 23 pairs of chromosomes, which contain DNA information for all the genes in the body’s cells. The chromosomes and information within them tell the cells how to grow and multiply.
When cells multiply, they make copies of themselves, taking all information from the cell — including these chromosomes — to the new cell. Sometimes during this process, the cells may make a mistake when copying their information to form a new cell.
The Philadelphia chromosome is one of these mistakes. It occurs when pieces of two different chromosomes swap places. This happens with parts of chromosomes 9 and 22, which break away and change places to make an abnormal chromosome 22 — the Philadelphia chromosome.
The presence of the Philadelphia chromosome in CML means the person has Philadelphia chromosome chronic myeloid leukemia (Ph+ CML).
Ph+ CML creates an abnormal gene called BCR-ABL. This gene produces an abnormal protein in the bone marrow called tyrosine kinase. This protein can activate the bone marrow, causing it to make too many immature white blood cells.
Normally, the body creates and uses immature white blood cells in a controlled way. However, with Ph+ CML, these immature white blood cells grow out of control. These cells can also contain the Philadelphia chromosome, which means the copies of these cells will also include it.
Doctors may call these cells leukemic white blood cells, which start to duplicate, build up in the bone marrow, and travel through the body via the bloodstream.
Over time, these cells may take the space of healthy white and red blood cells and platelets, leading to a person experiencing physical symptoms.
Unlike other types of cancers, which occur in stages, doctors classify CML into phases. These phases refer to the spread and acceleration of the disease:
- Chronic phase: The abnormal cells are in the person’s blood, bone marrow, and spleen but are still in relatively low numbers of the blood.
- Accelerated phase: A phase of accelerated cell growth, as numbers of abnormal cells increase in the blood.
- Blastic phase: Cells progress to the lymph nodes and damage other tissues and organs, and make up a larger percentage of total blood.
Some doctors may also refer to a terminal phase of CML. This means the cells are widespread, and the person may only survive weeks or months.
Research from 2019 notes that about
Many people with Ph+ CML will not experience symptoms before their diagnosis. The first sign for many people may be a high white blood cell count during a routine blood test.
If symptoms do occur, they may include:
PH+ CML only occurs when the Philadelphia chromosome creates abnormal genes in the cells that lead to abnormal protein growth and abnormal white blood cells.
DNA changes from CML occur over a long period throughout a person’s lifetime. It is not clear what initially starts the process of this abnormal change.
CML is not genetic. A person cannot inherit it from a parent. As the
There is also no way to catch or contract Ph+ CML. There may be some risk factors for cancers, such as a history of radiation exposure.
CML occurs slightly more in males than females. It mainly affects people in their 40s, 50s, and 60s, though in some cases, it may affect younger people.
Doctors may first suspect an issue such as CML after performing a routine blood test. Bloodwork may show higher than normal levels of white blood cells, which doctors will use as a starting point to order more tests.
Other tests to help confirm a diagnosis may include:
- bone marrow biopsy
- bone marrow tissue sample
- fluorescence in situ hybridization (FISH)
- polymerase chain reaction (PCR)
- genetic testing
- cytogenetic analysis
The primary treatment for CML are drugs called tyrosine kinase inhibitors. These drugs block the tyrosine kinase that activates the overgrowth of blood cells. As these drugs target the specific mechanisms of the cancer, they may be better treatments than other forms of therapy, such as chemotherapy or bone marrow transplant.
A person can discuss the various types of tyrosine kinase inhibitor drugs with their doctor, each with different possible side effects and effectiveness. Tyrosine kinase inhibitors include:
Doctors may also recommend other treatments. These may include drugs to inhibit bone marrow, chemotherapy, or radiative therapy for the spleen.
If CML is detected very early on, a bone marrow transplant may be an option for some people. In some cases, this may lead to complete remission and cure.
The phasing will also play a role in CML treatment. People with accelerated phase CML may need more aggressive treatments or different drugs to control the disease.
Experimental treatments or clinical trials may also be available in some cases. People can talk with their doctor to consider all options.
The National Cancer Institute notes the median survival rate for CML is
For instance, a 2020 study examining the use of a drug called imatinib (Gleevec) in low- and middle-income countries reported that the 5-year survival rate of people receiving this drug was 92% for those with chronic phase CML.
However, it is very difficult to gauge an individual’s survival rate, as many factors play a role, including:
- age at diagnosis
- spleen involvement
- platelet count
- overall percentage of blood affected
- other chromosome changes
- response to treatments
- other health conditions
Detecting the cancer as early as possible may give the person more treatment options. In some cases, doctors may recommend trials or experimental treatments as a way to improve outcomes.
Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) causes abnormal changes to the chromosomes that lead to high levels of abnormal cells in the bone marrow and blood. Left untreated, the overgrowth of these cells may lead to complications of CML, especially in later stages.
Routine bloodwork can help detect early signs of the disease, such as high white blood cell count. Detecting the disease early on provides the best outlook and treatment options. Working closely with a doctor to find the ideal treatments available for their specific case may give a person the best outlook.