What is Chronic Myelogenous Leukemia – Philadelphia Chromosome Translocation, Symptoms, Diagnosis and Treatment

Exposure to ionizing radiation can cause abnormal and rapid growth of white blood cells in bone marrow and blood. The condition is a cancer type technically known as

chronic myelogenous leukemia (CML)

. Every year, it affects 1-2 per 100,000 people especially in their middle-age or later years. Men are slightly more at risk of developing this cancer when compared to women. This article tries to gain further insight on this subject.

What is Philadelphia Chromosome Translocation?

In 95 percent CML patients, this abnormal genetic event is diagnosed. Any cell in the human body has a central section called nucleus. Inside this component, genetic materials called DNA and RNA molecules are present.

The DNA molecule form chemical structures called chromosomes. These are the instructions which any cell follows to carry out its tasks. Set of chromosomes form a gene. The RNA molecule reads a gene and produces a substance called protein which actually carries out the specific task of a cell. This is called gene expression.

Probably due to several uncontrollable environmental influences, some times, parts of chromosomes interchange their positions. Such an event (technically known as chromosome translocation) completely changes the specific instructions to be followed by cells owing to the alteration in their structures.

CML is caused when translocation takes place between parts of the chromosome 9 (Abl1 gene) and chromosome 22 (BCR gene). This abnormal event is known as

Philadelphia chromosome translocation


Generally, chromosomes are uniform structures in length. But, when the mentioned abnormality takes place, the length of the chromosome 9 increases and chromosome 22 becomes shorter. This gives rise to a process called gene fusion. Here, BCR gene binds with Abl1 gene creating a new and hybrid gene called the BCR-ABL gene of cancer. The new gene gets attached to the shorter chromosome 22 to compensate for its shorter length.

The protein produced by this rogue gene is called Bcr-abl fusion protein. It in turn initiates production of several proteins and enzymes which cause the white blood cells to grow rapidly in the bone marrow and latter in the blood. It is constitutionally active which means that it does require any activation agent to start functioning. It also inhibits any attempt made by the body to address the crisis by stopping the DNA repair.

Symptoms of Chronic Myelogenous Leukemia:

  • Asymptomatic or without any signs in the initial stages
  • High levels of white blood cells diagnosed through laboratory tests
  • Swelling of the spleen causing pain on the left side
  • Hip pain
  • Joint pain
  • Malaise
  • Low grade fever
  • Increased susceptibility to infection
  • Low count of the red blood cells
  • Low count of the platelets in blood
  • Bruising

The mentioned signs of

chronic granulocytic leukemia CGL

(other name of this cancer) become apparent in three different phases of this disease. The term chronic in the name of the disease implies that the cancer grows over a period of time and the signs are apparent periodically. The phases of CGL are namely, chronic, accelerated and blast phase.

Chronic Phase:

Nearly 85 percent people are found to be in this phase at the time of diagnosis.

The signs are:

  • Asymptomatic
  • fatigue
  • hip pain
  • joint pain
  • pain in the left side of the spleen
  • abdominal fullness

Depending on how early these signs are diagnosed, the duration of phase this varies. If the signs are ignored, the cancer progresses to the next stage.

Accelerated Phase:

According to the World Health Organization, the criteria of diagnosis of this phase are:

  • Presence of a type of stem cells called myeloblasts in the blood and bone marrow found in 10-19 percent patients
  • Presence of white blood cells in the bone marrow and blood found in more than 20 percent patients
  • Count of platelets less than 100,000 without any therapy
  • Count of platelets exceeding 100,000 and not responding to therapy
  • More genetic abnormalities apart from Philadelphia chromosome translocation
  • Enlargement of the spleen

Diagnosis of any of the above mentioned signs means that the patient is in the accelerated phase of CGL and the cancer would definitely progresses to the blast phase. Here, treatments prove ineffective.

Blast Phase:

This is the final stage of the cancer characterized by rapid progression of the rogue cells to remote and fresh locations of the body and unfortunately short survival time left for the patient. By this stage:

  • There are more 20 percent myeloblasts in the bone marrow and blood
  • Solid tumors known as chloroma develop outside the bone marrow
  • Biopsy diagnostic technique reveals large cluster of blasts around the bone marrow

Diagnosis of Chronic Granulocytic Leukemia (CGL):

Complete blood count test reveals the abnormal presence of white blood cells and other components of blood. Bone marrow biopsy is also performed to confirm the same. A cytogenetic technique known as fluorescent in situ hybridization confirms

Philadelphia chromosome translocation

abnormality of the genes.

Treatment of Myelogenous Leukemia in Chronic Phase:

Treatment is futile for accelerated and blast phase of CGL. But, advancement in understanding the origin of the cancer has lead to the early diagnosis of this cancer in its chronic phase.

Remedies technically known as targeted therapies like imatinib, nilotinib and dasatinib are now available which have improved the survival rate close to 90 percent.

The Food and Drug Administration approved imatinib in 2001. To overcome the resistence of this drug, two new medicines Nilotinib and Dasatinib were later developed. They were also approved as first-line therapy for

chronic myelogenous leukemia

in 2010. All these three drugs work by inhibiting the cancerous actions of Bcr-abl fusion protein.

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