WHAT IS CML?
Chronic myelogenous leukemia (CML, also called chronic myeloid leukemia) or chronic
granulocytic leukemia (CGL) is a disease afflicting 1.4 in 100,000 people. In the US, new
cases of CML are diagnosed every year and it forms 14% of all leukemias diagnosed. The
disease arises from an abnormal stem cell in the bone marrow and is characterized by
increased proliferation of leukemic cells. These cells do not die when they are meant to
resulting in a buildup of leukemic cells in the marrow, in the blood, in the liver and spleen. A
normal white blood count should be 5000 to 10,000. In a patient diagnosed with CML, the
white blood count raises anywhere between 50,000 to 500,000, which is 5-50 times the normal
upper limit of white blood count and at diagnosis, it is estimated that there could be up to one
trillion leukemia cells.
A patient can be diagnosed in three different stages of CML (see CML disease stages) and if
untreated, the disease can progress to a terminal blastic stage. CML can be cured by a bone
marrow transplant from a fully matched donor and in the present day, can be treated with
excellent drugs which controls the disease long-term.(see CML treatments)
CML is caused by the exchange of genetic materials between two of our chromosomes. We
have 46 chromosomes inherited from our parents. In CML patients, there is an acquired
genetic defect when two chromosomes, chromosome 9 and chromosome 22 undergo a
balanced reciprocal translocation or crisscrossing of two pieces of genetic materials, one on
chromosome 9 and one on chromosome 22. During cell division, the two chromosomes criss-
cross, break and fuse to each other. The ABL gene part of chromosome 9 exchange with the
BCR gene part of chromosome 22, resulting in a shortened chromosome 22, now called the
Philadelphia chromosome or Ph chromosome. Chromosome 9 grows longer after the
exchange and is called derivative chromosome 9. As a result of this break away of genetic
material and fusion, a oncogene is formed that was not there before. This is called the BCR-
ABL fusion gene.
The BCR-ABL gene in turn forms a BCR-ABL oncoprotein (p210 protein). This abnormal
protein or enzyme is called a tyrosine kinase. Tyrosine kinases are signal transducers asking
the cells to grow and if the signal transduction protein is constantly in the “on” position, the cell
constantly grows akin to a light switch that has got turned on and there is no turning off. This
is how leukemic white blood cells grow and proliferate giving rise to the cancer.
In the bone marrow report of CML patients, the Ph translocation is depicted as t(9;22)(q34;
q11). 90% of patients will have this hallmark of CML, the Ph chromosome. In a small minority
of patients, this chromosome is masked but a FISH test can detect the BCR-ABL gene fusion
signal. This subset of CML is called Ph negative BCR-ABL positive CML. Another small
minority of patients are diagnosed with the Ph chromosome masked and BCR-ABL fusion
gene is also not detected. This type of CML is called atypical CML and is more difficult to treat.
Chronic myelogenous leukemia (CML, also called chronic myeloid leukemia) or chronic
granulocytic leukemia (CGL) is a disease afflicting 1.4 in 100,000 people. In the US, new
cases of CML are diagnosed every year and it forms 14% of all leukemias diagnosed. The
disease arises from an abnormal stem cell in the bone marrow and is characterized by
increased proliferation of leukemic cells. These cells do not die when they are meant to
resulting in a buildup of leukemic cells in the marrow, in the blood, in the liver and spleen. A
normal white blood count should be 5000 to 10,000. In a patient diagnosed with CML, the
white blood count raises anywhere between 50,000 to 500,000, which is 5-50 times the normal
upper limit of white blood count and at diagnosis, it is estimated that there could be up to one
trillion leukemia cells.
A patient can be diagnosed in three different stages of CML (see CML disease stages) and if
untreated, the disease can progress to a terminal blastic stage. CML can be cured by a bone
marrow transplant from a fully matched donor and in the present day, can be treated with
excellent drugs which controls the disease long-term.(see CML treatments)
CML is caused by the exchange of genetic materials between two of our chromosomes. We
have 46 chromosomes inherited from our parents. In CML patients, there is an acquired
genetic defect when two chromosomes, chromosome 9 and chromosome 22 undergo a
balanced reciprocal translocation or crisscrossing of two pieces of genetic materials, one on
chromosome 9 and one on chromosome 22. During cell division, the two chromosomes criss-
cross, break and fuse to each other. The ABL gene part of chromosome 9 exchange with the
BCR gene part of chromosome 22, resulting in a shortened chromosome 22, now called the
Philadelphia chromosome or Ph chromosome. Chromosome 9 grows longer after the
exchange and is called derivative chromosome 9. As a result of this break away of genetic
material and fusion, a oncogene is formed that was not there before. This is called the BCR-
ABL fusion gene.
The BCR-ABL gene in turn forms a BCR-ABL oncoprotein (p210 protein). This abnormal
protein or enzyme is called a tyrosine kinase. Tyrosine kinases are signal transducers asking
the cells to grow and if the signal transduction protein is constantly in the “on” position, the cell
constantly grows akin to a light switch that has got turned on and there is no turning off. This
is how leukemic white blood cells grow and proliferate giving rise to the cancer.
In the bone marrow report of CML patients, the Ph translocation is depicted as t(9;22)(q34;
q11). 90% of patients will have this hallmark of CML, the Ph chromosome. In a small minority
of patients, this chromosome is masked but a FISH test can detect the BCR-ABL gene fusion
signal. This subset of CML is called Ph negative BCR-ABL positive CML. Another small
minority of patients are diagnosed with the Ph chromosome masked and BCR-ABL fusion
gene is also not detected. This type of CML is called atypical CML and is more difficult to treat.
