Leukemia is a malignant disorder of the blood and blood forming organs such as the bone

marrow, spleen and the lymph system . Bone marrow is the site of proliferation of the cell it is
located inside the bone. Inside this bone marrow are where the cells proliferate or are “born”
Hemoptaeisis is the process in which blood cell is formed. With in the bone marrow is where the
stem cells located. The stem cell have the ability to self replicate ensuring a continuous supply of
stem cells now this stem cells when stimulated they undergo a process called differentiation into
either myeloid or lymphoid. Myeloid stem cells differentiate into 3 broad cell types as you can
see there in the illustration it can be erythrocytes,leukocytes and the platelets and the Lymphoid
can differentiate into T lymphocytes, B lymphocytes.
Now in leukemia there is an uncontrolled proliferation of leukocytes which causes overcrowding
of bone marrow and because of the overcrowding of the leukocytes bone marrow decreases the
production and function of normal hematopoietic cells.

Risk factors for leukemia

Exposure to radiation
Which explains how leukemia can sometimes develop as a secondary cancer after an aggressive
radation therapy and the treatment of unrelated cancer
Exposure to formaldehyde and the chemical benzene
This is found in smoke from the cigarretes and benzene is found in gasoline can alter the genes
The risk of also developing leukemia is raised when you have a rare genetic disorder such as the
down syndrome or trisomy 21.
Those with down syndrome has 3 copies of chromosome 21 instead of just 2 and this
overexpression of genes increases the risk of developing leukemia

Pathophysio

Normally, the body makes  blood stem cells (immature cells) An immature cell that can develop
into all types of blood cells, including white blood cells, red blood cells, and platelets. Also
called hematopoietic stem cell.become mature blood cells over time. A blood stem cell may
become a myeloid stem cell or a lymphoid stem cell.
A myeloid stem cell becomes one of 4 types of mature blood cells:
Erythrocytes,granulocytes and agranulocytes like monocytes and megakaryocytes which
platelets come from

 Red blood cells that carry oxygen and other substances to all tissues of the body.

 White blood cells that fight infection and disease.
  Platelets that form blood clots to stop bleeding.
A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes 
 B lymphocytes that make antibodies to help fight infection.
 T lymphocytes that help B lymphocytes make antibodies to fight infection.
Now this are important in adaptive immunity
Natural killer cells that attack cancer cells and viruses. Part of innate immunity
Now this is the normal process of proliferation and differentiation and it is called the
hematopoiesis this is continuously happening however sometimes a certain cell in the process
fails to differentiate and this abnormal cell continuously proliferate this breach or disruption may
occur when there is a translocation,inversion or deletion of a gene that are involve in controlling
the regulation of blood cell growth and development. leukemia comes when there is a high level
of blast cell ( blast cell are undifferentiated cell ). Genetic abnormalities disrupts the
differentiation of the cell to the terminal function of the cell and along where the disruptions
occur partially determines which type of leukemia a person. A breach of differentiation of the
myeloid cell line is called myeloid leukemia and if its on the lymphoid cell line it is called
lymphoid leukemia. Now this types of leukemia have both acute and chronic types. If the breach
occurs in the immature cells or the blast cell it is called acute now in this area where the blast
cells are this are all undifferentiated and functionless. If the breach occurs within the later or
nearly matured cells the leukemia will be chronic. When there is a proliferation of the blast cell
there will be less space and energy available in the production of leukocytes and lymphocytes
and platelets this is why both types of leukemia can manifest with low rbc count, low/abnormal
white blood cell count as well as low platelets count.
When there is a decrease blood oxygen levels it can lead to fatigue,muscular weakness, shortness
of breath and pallor. Because we also have low/abnormal white blood cell count this decreases
the body’s ability to fight infections and lastly because there is a low platelets count we all know
the function of platelets this helps the body to clot. Decrease in blood clotting occurs that’s why
you can observe symptoms such as bleeding gums,petechiae ecchymosis are all symptoms
associated with thrombocytopenia. The leukemic cells continues to proliferate in the bone
marrow putting pressure on the bone marrow causing bone marrow expansion which causes bone
pain and tenderness in bones and joints. eventually the leukemic blast cell or this immature
precursor cells which are normally never out in the bone marrow leaks into the blood circulation
and this causes increase blood viscosity. Leukostasis occur when the blood blast count is at or
greater than 100,000 cells per microliter because of this blood becomes really thick which causes
slow circulation through out the body which increases blood vessel obstruction.
Additional knowledge
Leukemia is caused by abnormalities in genes that controls the regulation of blood cells growth
and development or in the negative feedback loops that keep blood cell growth within normal
range. 3 of the most common structural changes can bring about this dysregulation of genes
includes: translocations,inversions and deletions

Translocation occurs when a portion of one chromosomes is transferred to another chromosome

and vice versa. An inversion occurs when part of chromosomes is turned upside down and a
portion of chromosomes becomes reversed in order a deletion occurs when part of the
chromosomes is lost.
One of the most studied translocation is the Philadelphia chromosomes which is seen in 90% of
those who have chronic myelogenous leukemia or cml the Philadelphia chromosomes forms
when breaks at the end of the chromosome 9 and 22 allowed the ABL-PROTOONCOGENE ON
CHROMOSOME 9 TO BE TRANSLOCATED TO THE BREAKPOINTS CLUSTER region
or BCR on chromosome 22 this reciprocal translocation produces BCR-ABL and the
Philadelphia chromosomes. BCR-ABL codes for a protein that allows effective cells to bypass
the regulatory signals controlling normal cells growth and differentiation thus resulting in
malignant transformations to become leukemic cells which causes the pathogenesis of CML.
THE BCR-ABL protein is a tyrosine kinase this means that it has the ability to transfer a
phosphate group from ATP to another structure this process is known as phosphorylation in this
case BCR-ABL transfers a phosphate group to a cancer protein causing it to become activated
which leads to uncontrolled myeloid growth and brings about cml.

Medical Management on AML

The choice of agents is based on the patient's physical status and history of prior antineoplastic
treatment. Older patients (especially those older than 70 years) tend to not tolerate standard therapy.
Lower-intensity therapy (using hypomethylating agents, low doses of cytarabine, or

hydroxyurea) may extend survival somewhat without a significant increase in toxicity beyond that of the
underlying disease

. Treatment of AML revolves around induction therapy using the differentiating agent all-trans retinoic
acid (ATRA), which inhibits the blast cells to differentiate, which reduces the blasts from proliferating at
an immature stage. ATRA is typically combined with a formulation of arsenic (arsenic trioxide) and, in
those deemed to be at high risk for relapse,

In AML, the aim of induction therapy is to eradicate the leukemic cells; however, this is also
accompanied by the eradication of normal types of myeloid cells. making, the patient becomes severely
neutropenic; an absolute neutrophil count of O is not uncommon. Anemia, and severe
thrombocytopenia (a platelet count of less than 5,000/mm), is also common. During this time, the
patient is typically very ill, with bacterial, fungal, and occasionally viral infections; bleeding; and severe
mucositis, which causes pain, diarrhea, and an inability to maintain adequate nutrition

When the patient has recovered from the induction therapy (i.e., the neutrophil and platelet counts
have returned to normal and any infection has resolved), consolidation therapy is given to eliminate any
residual leukemia cells that are not clinically detectable and reduce the chance for recurrence.

Multiple treatment cycles of various agents are used, usually containing some form of cytarabine.
Frequently, the patient receives one cycle of treatment that is almost the same as, if not identical to, the
induction treatment but at somewhat lower dosages. Because the amount of leukemia cells is
dramatically reduced at this point, toxicity associated with therapy is less (Schiffer, 2014).

Another aggressive treatment option is hematopoietic stem cell transplantation (HSCT). When a
suitable tissue match can be obtained, the patient goes on an even more aggressive regimen of
chemotherapy (sometimes in combination with radiation therapy), with the treatment goal of
destroying the hematopoietic function of the patient's bone marrow. The patient is then "rescued" with
the infusion of the donor stem cells to reinitiate blood cell production.

Patients who undergo HSCT have a significant risk of infection and graft-versus host disease (where the
donor's lymphocytes [graft] recognize the patient's body as "foreign" and set up reactions to attack the
"foreign" host, i.e., the patient). The most appropriate use and timing of HSCT remain unclear. Patients
with a poorer prognosis may benefit from early HSCT; those with a good prognosis may not need
transplant at all.

Another important option for the patient to consider is supportive care alone. In fact, supportive care
may be the only option if the patient has significant comorbidity, such as extremely poor cardiac,
pulmonary, renal, or hepatic function; is older and frail; or both. Patients are more commonly supported
with antimicrobial therapy and transfusions as needed. This treatment approach provides the patient
with some additional time outside the hospital; however, death frequently occurs within months,
typically from infection or bleeding.

Tyrosine Kinase Inhibitor this blocks the signals within the leukemic cells that expresses BCR-ABL protein
and preventing a series of chemical reaction which causes the cell to grow and divide. Monitoring for the
patient is required since the the drug is common to drug-drug interactions . antacids and grapefruit juice
may limit the drug absorption and large doses of acetaminophen can cause hepatotoxicity.

CML

Chronic: This is the earliest phase of CML. The majority of CML patients are
diagnosed during this phase as a result of mild symptoms, particularly fatigue.

Accelerated: If CML has not responded to treatment well during the chronic phase, it
becomes more aggressive, which can lead to the accelerated phase. At this point,
symptoms may become more noticeable.
Blastic: This is the most aggressive stage of chronic myeloid leukemia. Blastic refers
to having more than 20 percent myeloblasts or lymphoblasts. Symptoms are similar
to those of acute myeloid leukemia.