Chronic Myeloid Leukemia

By Julia Curtiss
Period 1
 Basic Information
Chronic leukemia means cells mature partly
but not completely. These cells do not fight
infection as well as white blood cells do.
Leukemia cells live longer than normal cells,
build up, and crowd out normal cells in the
bone marrow. Often times, chronic leukemia
doesn’t present symptoms for many years
and are harder to cure than acute leukemias.

Chronic Myeloid Leukemia (CML) is a type of

cancer that starts in blood-forming cells of the
bone marrow. It is more common in adults
but in rare cases can develop in children.
 Causes and Risk Factors for Chronic Myeloid
Leukemia
● Changes in DNA (mutations) that turn on oncogenes or turn off tumor suppressor genes
○ Oncogenes: genes that promote cell growth and division
○ Tumor suppressor genes: genes that slow down cell division or cause cells to die at the
right time
○ Mutation: error in the copying process of DNA during cell division that affects the genes
and chromosomes in the copied DNA
● Radiation exposure
● Age (risk increases with age)
● Gender (more common in males than in females)
● Does not run in families
 Signs and Symptoms
● Weakness The symptoms of Chronic Myeloid Leukemia are
● Fatigue often vague and are more often than not caused by
● Night sweats other things. These signs and symptoms may also
● Weight loss apply to other cancers and conditions.
● Fever
● Enlarged spleen (felt as a mass under
the left side of the rib cage)
● Pain of sense of “fullness” in the belly
● Bone pain (caused by leukemia cells
spreading from the marrow cavity to the
surface of the bone or into the joint)
● Bruising
 Problems Caused by a Lack of Red Blood Cells
Many of the signs and symptoms of CML ● Neutropenia (level of normal neutrophils is low)
occur because the leukemia cells replace the increases risk of getting a serious bacterial
bone marrow’s normal blood-making cells. As infection.
a result people with CML don’t make enough ● Thrombocytopenia (shortage of blood platelets)
red blood cells, properly functions white blood leads to easier bruising or bleeding.
cells, and platelets.

● Anemia (shortage of red blood cells)

causes weakness, tiredness, and
shortness of breath.
● Leukopenia (shortage of normal white
blood cells) increases risk of infection.
Leukemia cells do not protect against
infection like normal WBCs do.
 Affected Gene
Each human cell contains 23 pairs of chromosomes.
Most cases of CML start during cell division, when
DNA is "swapped" between chromosomes 9 and 22.
Part of chromosome 9 goes to 22 and part of 22
goes to 9.
This gene then produces the BCR-ABL protein,
which is the type of protein called a tyrosine
kinase. This protein causes CML cells to grow and
divide out of control.

This is known as a translocation and it makes a

chromosome 22 that's shorter than normal. This new
abnormal chromosome is called the Philadelphia
chromosome which is found in the leukemia cells of
almost all patients with CML

The swapping of DNA between the chromosomes

leads to the formation of a new gene (an oncogene)
called BCR-ABL.
Cell Signaling
Pathway Involved:
Tyrosine-Kinase
 Normal Mechanism
A neighboring signaling molecule binds to the
receptor tyrosine kinase which will activate the
tyrosine kinase in the cytoplasmic tail of the
receptor. An ATP molecule loses a phosphate
group (becomes ADP+P). The phosphate is
attached to a tyrosine (kinase activity transfers
phosphate to tyrosine). Inactivated proteins
attach to phosphorylated tyrosine which
causes a structural change that stimulates a
signal transduction pathway generating a
cellular response. The protein then dimerizes
and becomes ready to enter the protein. The
dimer binds to a specific section of DNA,
promoting the translation of that area.
Tyrosine kinase plays a key role in the
regulation of cell growth, differentiation and
survival.
 Abnormal Mechanism
The fusion protein BCR-ABL produced by the
Philadelphia chromosome continuously
activates the tyrosine kinase ABL that would
normally only be activated when the cell is
stimulated by a growth factor.
Autophosphorylation events occur which
trigger the kinase and generate docking sites
for intermediary adaptor proteins such as
GRB2. BCR-ABL dependent signaling facilitates
activation of multiple downstream pathways
that enforce enhanced survival, inhibition of
apoptosis, and perturbation if cell adhesion
and migration.
 Current Direction of Research
● Treatment:
○ Targeted therapies (chronic phase). Uses drugs to identify and attack the cancer cells
without harming normal cells. Also called tyrosine kinase inhibitors and may be used in
early phases of CML.
○ Chemotherapy (accelerated phase). Drug that can be injected or taken orally, enters the
bloodstream and reaches all parts of the body. Treatment with conventional cytotoxic (cell-
killing) drugs that mainly kill cells that are growing and dividing rapidly.
○ Radiation therapy is not as common but can be used to treat pain from bone damage or
shrink the spleen using high-energy rays or particles to destroy cancer cells.
○ Stem cell transplant is the only treatment that provides a potential cure. After high doses
of chemotherapy, patients are infused with healthy, blood-forming stem cells donated by
another person with a nearly identical tissue type
○ Bone marrow transplants, only recommended for young patients and donor must ideally
be a close relative.
 Works Cited
Manash, Paul K, and Mukhopadhyay K Anup. “Tyrosine Kinase – Role and
Significance in Cancer.” International Journal of Medical Science, 2004,
www.medsci.org/v01p0101.htm

Bacco, Alessandra Di, et al. “Molecular Abnormalities in Chronic Myeloid Leukemia:

Deregulation of Cell Growth and Apoptosis.” The Oncologist, 1 Oct. 2000,
theoncologist.alphamedpress.org/content/5/5/405.full

“What Is Chronic Myeloid Leukemia? | Leukemia Types.” American Cancer Society,

www.cancer.org/cancer/chronic-myeloid-leukemia/about/what-is-cml.html