CHRONIC MYELOID LEUKEMIA

• DEFINITION

CML is a malignant clonal disorder of hematopoietic

stem cells that results in increases in not only myeloid cells
but also erythroid cells and platelets in peripheral blood
and marked myeloid hyperplasia in the bone marrow.

CML is a clonal bone marrow stem cell disorder in

which proliferation of mature granulocytes (neutrophils,
eosinophils, and basophils) and their precursors is the main
finding. It is a type of myeloproliferative disease associated
with a characteristic chromosomal translocation called the
Philadelphia chromosome.
• ETIOLOGY

The etiology of CML is unclear. Some associations with

genetic and environmental factors have been reported, but,
in most cases, no such factors can be identified.
1. Genetic factors
2. Environmental factors
Nuclear and radiation exposures, including therapeutic
radiation, have been associated with the development of
CML.
Chronic Myeloid Leukemia Initiated by the
translocation t(9;22) that produces the BCR/ABL fusion
tyrosine kinase. Constitutive activity of the BCR/ABL
enzyme is responsible for the unrestrained growth of CML
cells.
• PATHOGENESIS

CML was the first malignancy to be linked to a clear

genetic abnormality, the chromosomal translocation known
as the Philadelphia chromosome. In this translocation,
parts of two chromosomes (the 9th and 22nd by
conventional karyotypic numbering) switch places. The bcr-
abl fusion gene product is also a tyrosine kinase
As a result, part of the BCR ("breakpoint cluster
region") gene from chromosome 22 is fused with the ABL
gene on chromosome 9. The BCR-ABL transcript is
continuously active and does not require activation by
other cellular messaging proteins. In turn, BCR-ABL
activates a cascade of proteins which control the cell cycle,
speeding up cell division
• CLINICAL MANIFESTATION

Symptoms of CML may include: malaise, low-grade

fever, gout, increased susceptibility to infections, anemia,
and thrombocytopenia with easy bruising (although an
increased platelet count (thrombocytosis) may also occur in
CML). Splenomegaly may also be seen.
CML usually runs a biphasic or triphasic course. This
process includes an initial chronic phase and a terminal
blastic phase, which is preceded by an accelerated phase in
60% to 80% of patients.
Chronic phase Accelerated phase
Approximately 85% of The WHO criteria define the
patients with CML are in accelerated phase by any of the
the chronic phase at the following:
time of diagnosis. 1. 10–19% myeloblasts in the
During this phase, blood or bone marrow
patients are usually 2. >20% basophils in the blood
asymptomatic or have or bone marrow
only mild symptoms. 3. Platelet count <100,000,
unrelated to therapy
4. Platelet count >1,000,000,
unresponsive to therapy
5. Cytogenetic evolution with
new abnormalities in
addition to the Philadelphia
chromosome
6. Increasing splenomegaly or
white blood cell count,
unresponsive to therapy
Blast crisis
Blast crisis is the final phase
in the evolution of CML, and
behaves like an acute
leukemia, with rapid
progression and short
survival.[2] Blast crisis is
diagnosed if any of the
following are present in a
patient with CML:
1. >20% myeloblasts or
lymphoblasts in the
blood or bone marrow
2. Large clusters of blasts in
the bone marrow on
biopsy
• TREATMENT

The goal of chronic myelogenous leukemia treatment is to eliminate

the blood cells that contain the abnormal BCR-ABL gene that causes the
overabundance of diseased blood cells.
1. Targeted drugs
In chronic myelogenous leukemia, the target of these drugs is the
protein produced by the BCR-ABL gene — tyrosine kinase. Targeted drugs
that block the action of tyrosine kinase include Imatinib
(Gleevec),Dasatinib (Sprycel),Nilotinib (Tasigna).
2. Blood stem cell transplant (bone marrow transplant)
3. Chemotherapy
4. Biological therapy
The biological drug interferon is a synthetic version of an immune
system cell. Interferon may help reduce the growth of leukemia cells.
 GOUT
• DEFINITION
Gout is a disease that results from an overload of uric acid in the
body. Uric acid is a breakdown product of purines that are part of many
foods we eat. This overload of uric acid leads to the formation of tiny
crystals of urate that deposit in tissues of the body, especially the joints.
When crystals form in the joints, it causes recurring attacks of joint
inflammation (arthritis). Gout is considered a chronic and progressive
disease. Chronic gout can also lead to deposits of hard lumps of uric acid
in the tissues, particularly in and around the joints and may cause joint
destruction, decreased kidney function, and kidney stones.
• ETIOLOGY

Gout is often related to an inherited abnormality in the body to

process uric acid. Uric acid levels can become elevated by eating a lot of
purine-rich foods such as meats, by the overproduction of uric acid by the
body, or if the kidneys do not eliminate excess uric acid. When uric acid
reaches a certain level in the blood it precipitates out in the form of
monosodium urate crystals. In gout, the crystals are deposited in
connective tissue and joint spaces evoking intense inflammation.

Risk Factors of Gout.

There are several factors that may caused gout :
1. Genetic defect in metabolism, which cause overproduction and
retention of uric acid.
2. Kidney impairment that prevents normal elimination of uric acid.
3. Disease of the blood cells and blood forming organs, certain cancers.
4. Other factors such as alcohol abuse and a purine rich diet
• PATHOGENESIS
Gout occurs when crystals of uric acid, in the form of monosodium urate,
precipitate in joints, on tendons, and in the surrounding tissues.[4] These
crystals may then trigger a local immune mediated inflammatory
reaction.[4] The triggers for precipitation are not well understood. While
uric acid may crystallize at normal levels, it is more likely to do so as levels
increase.[4][16] Other factors believed to be important in triggering an acute
episode of arthritis include: cool temperatures, rapid changes in uric acid
levels, and acidosis.[17][18] The increased precipitation at low temperatures
partly explains why the joints in the feet are most commonly affected.[2]
Rapid changes in uric acid may occur due to a number of factors including:
trauma, surgery, chemotherapy, diuretics, and stopping or starting
allopurinol.[1]
• CLINICAL MANIFESTATION

1. Recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen

joint)
2. Spiked rods of uric acid (MSU) crystals photographed under a microscope with
polarized light from a synovial fluid sample
3. Blood tests
Hyperuricemia is a classic feature of gout. Hyperuricemia is defined as a plasma
urate level greater than 420 μmol/L (7.0 mg/dL) in males and 360 μmol/L
(6.0 mg/dL) in females.

A definitive diagnosis of gout is based upon the identification of

monosodium urate (MSU) crystals in synovial fluid or a tophus.[3] Under polarized
light microscopy they have a needle-like morphology and strong negative
birefringence.
• TREATMENT
The initial aim of treatment is to settle the symptoms of an acute
attack (nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine and
steroids[2] ).[2] Repeated attacks can be prevented by different drugs used
to reduce the serum uric acid levels.[2] Ice applied for 20 to 30 minutes
several times a day decreases pain.[2][3] Avoiding or restrict foods high in
purine always be suggested to this patients.
THE CORRELATION BETWEEN CHRONIC
MYELOID LEUKEMIA AND GOUT
Myelogenous leukemia and gout, two distinct diseases of different etiology,
have in common disorder of uric acid metabolism which is manifested clinically by
an elevation of the blood uric acid.

Chronic myelogenous (or myeloid) leukemia (CML), also known as chronic

granulocytic leukemia (CGL), is a cancer of the white blood cells. The term
“myelogenous” im chronic myelogenous leukemia refers to the type of cells
affected by this cancer. Chronic myelogenous (or myeloid) leukemia it is a form of
leukemia characterized by the increased and unregulated growth of predominantly
myeloid cells (granulocytes, monocytes, erythrocytes, platelets) in the bone
marrow and the accumulation of these cells in the blood. The accumulation of
those immature cells in the blood commonly rubbing each other and susceptible
to be divided, because of that it will be much easier to them to be catabolism.
 The massive catabolism of those immature cells will results the catabolism
of purine, which is one of the components in nucleic acid that is within the cells.
Purine will be catabolism to hypoxanthine, then xanthine. Xanthine will be
oxidased by xanthine oxidase and become uric acid. Uric acid is the terminal
catabolic product of purine metabolism in humans.

Uric acid is more toxic to tissues than either xanthine or hypoxanthine.

Normally uric acid stays in solution in the blood. It moves through the circulation,
gets filtered by the kidneys, and it excreted in the urine. But in this disease,
because of the massive catabolism of the cells build up uric acids in the blood
stream, a condition known as hyperuricemia.

Hyperuricemia doesn’t always cause gout. Gout occurs when the sharp uric
acid crystal accumulate in the synovial fluid of the joint. In response to the
irritation caused by the uric acid crystal, the skin covering the affected area rapidly
becomes tight, inflamed, swollen, and red. It happens because white blood cells
recognizing the uric acid crystal and flood into the joint and surround the crystals
which cause inflamation.

The classical signs of inflammation, together with sudden and extreme pain,
strongly suggest an acute attack of gout. The diagnosis is confirmed by laboratory
findings of uric acid crystals in fluid taken from the affected joint.