Definition Hematopoiesis Types of Leukemia Acute Leukemias Chronic Leukemias Myeloid Leukemias Lymphoid Leukemias Causes and Risk
Factors Common Features Complications Leukemia vs. Lymphoma Prognosis
Vikkineshwaran
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Leukemia
Cancer of blood-forming cells in the bone marrow. These unstable, immature cells accumulate in the blood and within organs of the body. They are not able to carry out the normal functions of blood cells.
Blood
Normal blood contains 3 major groups of cells: red blood cells (erythrocytes) white blood cells (leukocytes) Platelets (thrombocytes) All 3 types of blood cells develop from one immature cell type in a process called haematopoiesis. Hematopoiesis= formation of
The stem cell divides and develops to a more developed, but still immature precursor, called a blast, which then develops through several more stages, into a mature blood cell.
This process takes place in the bone marrow, which is the soft spongy material found in the centre of most bones.
Stem Cell Maturation
The first step in the process of stem cell maturation is differentiation into 2 groups:
myeloid stem cell line:
Forms into RBC, platelets and certain types of WBC (monocytes/ granulocytes)
lymphoid stem cell line:
forms into lymphocytes (another type of WBC)
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Myeloid Stem Cell Line
Lymphoid Stem Cell Line
Blood Cell Development
Either lineage can be affected by leukemia.
Affecting the myeloid lineage myelocytic leukemias
myelogenous, myeloblastic, or nonlymphocytic
Affecting the lymphoid lineage lymphocytic leukemias.
lymphoblastic or lymphogenous
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Development of Leukemia in the Bloodstream
Stage 1- Normal
Stage 2- Symptoms
Stage 3- Diagnosis
Legend
White Cell Red Cell Platelet Blast Germ
Stage 5a- Anemia
Stage 4- Worsening
Sources from Leukemia, by D. Newton and D. Siegel
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Stage 5b- Infection
Classification of Types
Lineage + Duration
Lineage: Duration Forms Myelogenous
Lymphocytic Acute Chronic
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Acut Chroni e c
Myeloid Lymphoi d
AML
adult adult
CML CLL
adult
ALL
children
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Leukemia
Abnormal stem cells in bone marrow
Acute Leukemias
Blasts predominate Children or elderly Short & drastic course
Chronic Leukemias
More mature cells Midlife age range Longer, less devastating course
ALL
Lymphoblasts (pre-B or Pre-T)
CLL AML
Myeloblasts Lymphocytes Non-antibody producing B cells
CML
Myeloid stem cells Blast crisis
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Incidence of different types of leukemias according to age. ALL is predominantly a childhood disease & CLL occurs mainly in the elderly. AML and CML have a wider age distribution. 16
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Acute Leukemia
Short course of symptoms Fatigue, fever, easy bruising, bleeding Cytopenias - or pancytopenia
Cytopenia= reduction in the number of blood cells
Acute forms of leukemia can occur in children and young
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Acute
Rapid growth of immature blood cells. More than 20% blasts in bone marrow Blasts in peripheral blood in 90% cases This crowding makes the bone marrow unable to produce healthy blood cells.
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Immediate treatment is required in acute leukemias due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. If left untreated, the patient will die
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Acute Leukemias
acute lymphoblastic leukaemia (ALL): childhood acute myeloblastic leukaemia (AML): adults
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Chronic Leukemia
Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group. Most are asymptomatic at presentation Strikingly elevated WBC Marked left-shift Splenomegaly typical Lymphocytosis 23
Chronic
The excessive build up of relatively mature, but still abnormal, blood cells. Typically taking months to years to progress, The cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood.
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Acute Myelogenous Leukemia
Most common type of Leukemia Fast growing cancer of the blood and bone marrow Characterized by
Myelogenous Leukemia: AML vs. CML
Chronic Myelogenous Leukemia
Slow growing cancer of white blood cells 3 Phases
Chronic Accelerated Blast Phase (Sometimes referred to as ALL)
Leukemia cells in the Bone Marrow Blast cells- increased proliferation
Characterized by
Too many white blood cells Philadelphia chromosome t(9;22) bcr/abl gene Makes tyrosine kinase 25
Acute Lymphocytic Leukemia
Lymphocytic Leukemia: ALL vs. CLL
Chronic Lymphocytic Leukemia
Risk associated with CLL increases rapidly after age 40.
90% Diagnosed over age 50
Greatest risk for ALL is in the first 5 years of life Fast growing cancer of the blood and bone marrow Characterized by
Uncontrollable and exaggerated growth of lymphoblasts
Also non-functional
Can be a very stable disease, some may not received treatment directly after the diagnosis Characterized by
Staging system (Rai or Binet) # of lymphocytes in blood and marrow Spleen size Lymph node distribution
Blockade of normal marrow cells
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Causes and Risk Factors
There is no single known cause for all of the different types of leukemia. Four possible causes:
natural or artificial ionizing radiation, certain kinds of chemicals, some viruses, genetic predispositions.
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Genetic Predispositions
Leukemia, like other cancers, result from,
somatic mutations in the DNA which activate oncogenes or deactivate tumor suppressor genes, and disrupt the regulation of cell death, differentiation or division.
Mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances and are likely 28
Common features of Leukemia
diffuse replacement of normal bone marrow by leukemic cells with variable accumulation of abnormal cells in the peripheral blood infiltration of organs such as liver, spleen, lymph nodes, meninges and gonads by leukemic cells
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Complications of Leukemia
infection (leukocytopenia), haemorrhage (thrombocytopenia), anemia
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Lymphoma
A type of Cancer that begins with a malignant change in a lymphocyte, lymph node cell or lymphatic tissue of the marrow.
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2 main categories
Hodgkins Non-Hodkins
12% of Lymphoma One of the most curable Presence of ReedSternberg cell
Distinctive Blymphocytes
Majority of lymphoma cases
4 types of B-cell Other types are T-cell and NK cell
Spreads through the lymphatic system in a
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Leukemia vs. Lymphoma
Both Lymphocytic Leukemia and Lymphoma are the result of a malignant transformation of a cell destined to be a lymphocyte.
Distinction(s)
Lymphoma: The disease started from a lymphocytic cell in a lymph node or other part of the Lymphatic System (LS) Leukemia: The disease started from a lymphocytic cell in Bone marrow (BM)
In either case, the malignant cells can migrate from their source (BM or LS) and be found in34 the
Prognosis
Acute leukemia must be treated immediately, But chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy.
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P g o ic ro n st Fact o r
Su iv rv al
5 year sur vival is 1 0 -3 5 %for all pat ient s wit h AML AML 5 -1 0 %will sur vive mor e t han 5 year s 2 0 -3 5 %for young pat ient s who under go chemot her apy and BMT C hildr en AL L Adult s C ML St age O St age I C L L St age II St age III and IV 2 5 -3 5 %5 -year sur vival Median sur vival 5 -6 year s > 1 5 year s 9 year s 5 year s 2 year s
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6 0 -7 0 %5 -year disease fr ee sur vival
Died of Myelodysplastic syndrome (MDS) aka Pre-leukemia which later develops to AML
Marie Curie
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