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1
It is is a malignant disease characterized by unregulated proliferation of one cell type. It may involve any of the cell lines or a stem cell common to several cell lines.
Leukemia
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Leukemias are classified into these 2 major groups
Chronic leukemia, Acute leukemia
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Type of leukemia in which the onset is insidious, the disease is usually less aggressive, and the cells involved are usually more mature cells
Chronic leukemia
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Type of leukemia in which the onset is usually rapid, the disease is very aggressive, and the cells involved are usually poorly differentiated with many blasts
Acute leukemia
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Both acute and chronic leukemias are further classified according to the prominent cell line involved in the expansion: If the prominent cell line is of the myeloid series it is a ____________ leukemia (sometimes also called granulocytic) If the prominent cell line is of the lymphoid series it is a _____________leukemia
myelocytic, lymphocytic
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What are four basic types of leukemia?
Acute myelocytic leukemia (AML), Acute lymphocytic leukemia (ALL), Chronic myelocytic leukemia (CML), Chronic lymphocytic leukemia (CLL)
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Includes myeloblastic, promyelocytic, monocytic,myelomonocytic, erythrocytic, and megakaryocytic
Acute myelocytic leukemia - AML-
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It includes T cell, B cell, and Null cell
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It includes myelocytic and myelomonocytic
Chronic myelocytic leukemia - CML
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It includes plasmocytic multiple myeloma, Hairy cell, prolymphocytic, large granular cell lymphocytic, Sezary's syndrome, and circulating lymphoma.
Chronic lymphocytic leukemia - CLL
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The exact cause is frequently not known, but predisposing factors are known.
Etiology
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Predisposing factors to Leukemia/Etiology
Host factors, Environmental factors
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They can occur in all age groups
Acute leukemias
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They are usually a disease of adults
Chronic leukemias
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It is more common in children
Acute lymphocytic leukemia
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It is more common in adults
Acute myelocytic leukemia
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It is extremely rare in children and unusual before the age of 40
Chronic lymphocytic leukemia
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It has a peak age of 30-50
Chronic myelocytic leukemia
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What are the Environmental factors of Leukemia/Etiology?
Exposure to ionizing radiation, Exposure to mutagenic chemicals and drugs, Viral infections
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Some individuals have an inherited increased predisposition to develop leukemia
Host factors
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Comprehend!
.
22
It is the most immature cell that can be recognized as committed to a particular cell line.
Blast
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•Malignant transformation of a stem cell leading to unregulated proliferation and •Arrest in maturation at the primitive blast stage.
Acute leukemia
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What are the Clinical features of Acute leukemia?
Leukemic proliferation, accumulation, and invasion of normal tissues, including the liver, spleen, lymph nodes, central nervous system, and skin, cause lesions ranging from rashes to tumors.
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A ___________________ from the leukemic cells may inhibit proliferation of normal cells.
Humoral mediator
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Failure of the bone marrow and normal hematopoiesis may result in what?
Pancytopenia with death from hemorrhaging and infections.
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The Lab diagnosis of Leukemia is based on these two things
•Finding a significant increase in the number of immature cells in the bone marrow including blasts, promyelocytes, promonocytes (>30% blasts is diagnostic), •Identification of the cell lineage of the leukemic cells
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Increased WBCs due to blasts
Leukemic
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Blast without increased WBCs
Subleukemic
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Decreased WBCs with no blasts
Aleukemic
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Involvement of Peripheral blood in Leukemia
Anemia, Decreased platelets, Variable WBC count
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Classification of the immature cells involved may be done by what?
Morphology, Cytochemistry, Immunologic markers, Cytogenetics
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They are a pink staining, splinter shaped inclusion due to a rod shaped alignment of primary granules found only in myeloproliferative processes
Auer rod
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It is a large blast with a moderate amount of cytoplasm, fine lacey chromatin, and prominent nucleoli. 10-40% of it contain auer rods.
Myeloblast
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It is a small blast with scant cytoplasm, dense chromatin, indistinct nucleoli, and no auer rod
Lymphoblast
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It help to classify the lineage of a leukemic cell (myeloid versus lymphoid)
Cytochemistry
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It is found in the primary granules of granulocytic cells starting at the late blast stage.
Myeloperoxidase
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•It stains phospholipids, neutral fats and sterols found in primary and secondary granules of granulocytic cells and to a lesser extent in monocytic lysosomes. •Rare positives occur in lymphoid cells
Sudan black
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•It is used to identify monocytic cells which are diffusely positive. •T lymphocytes may have focal staining.
Nonspecific esterase
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Comprehend!
.
41
They may be found in myeloblasts and lymphoblasts. T lymphocytes have a high level of these and this can be used to help make a diagnosis of acute T-lymphocytic leukemia.
Acid phosphatase
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________________ have a high level of acid phosphatase and this can be used to help make a diagnosis of acute T-lymphocytic leukemia.
T lymphocytes
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It is located in the secondary granules of segmented neutrophils, bands and metamyelocytes.
Leukocyte alkaline phosphatase
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It is determined by counting 100 mature neutrophils and bands. Each cell is graded from 0 to 5. The total is calculated by adding up the scores for each cell.
LAP score
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These are used mainly for lymphocytes, i.e., for determining B cell or T cell lineage. These tests rely on antibodies made against specific surface markers.
Immunologic markers (immunophenotyping)
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In a direct assay, the primary antibody is ________________________.
Fluorescently labeled
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•This is a unique DNA polymerase present in stem cells and in precursor B and T lymphoid cells. •High levels are found in 90% of lymphoblastic leukemias. •It can also be detected using appropriate antibodies and flow cytometry.
Terminal Deoxytidyl Transferase
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High level of Terminal Deoxytidyl Transferase are found in where?
90% of lymphocytic leukemias
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It can now be used for diagnosis and for prognosis of hematologic malignancies.
Cytogenetics
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These tests are very useful for following the course of the disease
DNA based test
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It is usually associated with a better prognosis
A normal karyotype
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-This is the most common form found in children and it has the best prognosis. -The cell size is small with fine or clumped homogenous nuclear chromatin and absent or indistinct nucleoli.
L1
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-The nuclear shape is regular, occasionally clefting or indented. -The cytoplasm is scant, with slight to moderate basophilia and variable vacuoles.
L1
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- This is the most frequent ALL found in adults. - The cell size is large and heterogenous with variable nuclear chromatin and prominent nucleoli.
L2
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- The nucleus is irregular, clefting and indented. - The cytoplasm is variable and often moderate to abundant with variable basophilia and variable vacuoles.
L2
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What are the classifications of Acute lymphoblastic leukemia based on the cytological features of the lymphoblasts?
L1, L2, L3
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- This is the rarest form of ALL. - The cell size is large, with fine, homogenous nuclear chromatin containing prominent nucleoli.
L3
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-The nucleus is regular oval to round. -The cytoplasm is moderately abundant and is deeply basophilic and vacuolated.
L3
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Acute lymphocytic leukemia may also be classified on the basis of immunologic markers into:
•Early pre-B ALL •Pre-B ALL •B ALL •T ALL •Null or unclassified ALL (U ALL)
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It lack B or T markers and may be the committed lymphoid stem cell.
Null or unclassified ALL (U ALL)
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It is primarily a disease of young children (2-5 years), but it can also occur in adults
ALL
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L3 is also called as what?
Burkitts leukemia
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Where does L1 occurs?
In children
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It has a cure rate of 70%
B cell Acute lymphocytic leukemia
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True/False: Patients younger than 1 and greater than 13 have a poor prognosis
True
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This is a rare disorder characterized by extensive proliferation of megakaryoblast
Acute megakaryoblastic leukemia
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This is rare and is characterized by bone marrow having predominance of erythroblast
Erythroleukemia