INTRO TO LEUKEMIA Flashcards
1
Q
▪ a disease of the blood-forming tissues, predominantly the bone marrow
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LEUKEMIA
2
Q
• adults:
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bone marrow
3
Q
• children or newborns who develop early leukemic stages:
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liver and spleen
4
Q
▪ a malignant neoplasm characterized by disorderly (different maturation stages affected or arrested), purposeless (unwanted/unneeded response), and uncontrolled proliferation of one or more of the hematopoietic cells (due to gene mutation/oncogene activation and other factors affecting uncontrolled wbc production)
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LEUKEMIA
5
Q
▪ mutation of gene at a certain stage of [?] in a cell cycle
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DNA encoding
6
Q
▪ also caused by [?] in a cell cycle
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low or inhibition or regulatory cells/substances
7
Q
: regulates or suppresses activity of mutated gene/s or cells
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▪ regulatory substances
8
Q
: key regulators for cell proliferation
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• p27 and p53
9
Q
- very low levels or defective: mutated gene are allowed to proliferate
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• p27 and p53
10
Q
- leads to genetic mutation leading to leukemia
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• p27 and p53
11
Q
: master control during the transition stage of a primitive precursor cell until maturation
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▪ GATA2
12
Q
: arrests/halts cell maturation on a blast stage
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• GATA2 mutation
13
Q
: • causes the normal cells to be cancerous when mutated
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Proto-oncogenes
14
Q
Proto-oncogenes
• functions to encode proteins which stimulates:
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- cell division
- cell differentiation
- cell death (minimized or inhibit if unnecessary)
15
Q
• normal gene controlling essential cell functions such as signaling pathways, cell proliferation, differentiation, and apoptosis that, on mutation, may become an oncogene
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Proto-oncogenes
16
Q
• group of genes that causes the normal cells to become cancerous when mutated
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Proto-oncogenes
17
Q
Oncogene
• upon activation: exhibits increased production of an encoded protein which causes
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- increased cell division
- decreased cell differentiation
- inhibition of cell death (apoptosis)
18
Q
No cell death occurs with blast cells, allowing proliferation; no elimination of abnormal cells
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Oncogene
19
Q
Oncogene e.g.,
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DNMT3A
MEIS1
20
Q
(proto-oncogene; caused by viral infection)
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DNMT3A
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Q
(oncogene; triggers leukemia)
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MEIS1
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Q
• viruses have the capability to carry their own oncogene and mutating it to an individual’s proto-oncogene to their oncogenes with the use of triggers
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MEIS1
23
Q
- viruses integrate their RNA to our cells (nucleus) and their oncogene causes our proto-oncogene to become oncogene
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MEIS1
24
Q
IMPLICATED/ASSOCIATED CONDITIONS
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- HEREDITY/GENETIC
- CHROMOSOMAL ABNORMALITY/CONGENITAL FACTORS
- CHEMICAL AGENTS
- IONIZING RADIATION ]
- VIRUSES
- IMMUNOLOGICAL DEFECTS
- NEOPLASIA
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▪ All lines of the offspring may inherit the gene and demonstrate leukemia decelopment
1. HEREDITY/GENETIC
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2. CHROMOSOMAL ABNORMALITY/CONGENITAL FACTORS Examples:
• Trisomy 21
• Philadelphia (Ph) chromosome
• Chromosome 8 and 14 arm defects
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: most popular
- Ph1 chromosome
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ch22 abnormality
- Ph1 chromosome
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some part of ch9 is transferred to ch22 (modification)
- Ph1 chromosome
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usually seen mostly in CML and sometimes in ALL
- Ph1 chromosome
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3. CHEMICAL AGENTS
benzene
chloramphenicol
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most widely known to depress bone marrow
benzene
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antibiotic with major side effects or reversible bone marrow depression, aplastic anemia, and leukemia
chloramphenicol
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▪ used in chemotherapies to kill cancer cells
4. IONIZING RADIATION
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• not specific (usually systemic) and kills healthy cells thus aggravating the leukemic condition of a patient
4. IONIZING RADIATION
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▪ implicate the leukemic condition of a patient due to their mode of replication
5. VIRUSES
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• integrates their viral RNA causing the mutation or activation of proto-oncogene into oncogene in an infected individual
5. VIRUSES
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▪ most known virus to trigger leukemia
• Epstein-Barr virus (EBV)
• Human T-lymphotropic virus (HTLV) - HTLV-I - HTLV-II
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▪ breakdown (decreased capacity) of the immunosurveillance that normally keeps neoplastic growths, aggravating the leukemic condition
6. IMMUNOLOGICAL DEFECTS
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▪ usually seen in acute lymphocytic leukemia (ALL = prone to viral infections) and lymphoma
6. IMMUNOLOGICAL DEFECTS
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arise from the hematopoietic cells of bone marrow and usually spread first to peripheral blood
7. NEOPLASIA
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▪ cancerous cell clone will grow rapidly and at the expense of
normal hematopoietic cells
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CONSEQUENCES
▪ decreased RBC and platelet production (suppressed once there is a proliferation in 1 or 2 cell lines)
▪ deceased (blast cell are present in the circulation) to normal WBC production in peripheral blood (proliferation or increased production)
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OTHER SINGS AND SYMPTOMS
Anemia: fatigue, headache, dizziness
Neutropenia: fever, increased sweating
Thrombocytopenia: bleeding and clotting problems
Hypermetabolism
Organ Failure
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Anemia:
fatigue, headache, dizziness
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Neutropenia:
fever, increased sweating
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Thrombocytopenia:
bleeding and clotting problems
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▪ sign of bone marrow failure
Anemia
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▪ decreased RBC survival
Anemia
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▪ dyserythropoiesis (abnormal RBC production/structure/count)
Anemia
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dyserythropoiesis characterized by:
multinuclearity, gigantism (giant RBCs), pyknosis
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: hyperlobulated or hypolobulated nucleus with nuclear fragmentation
• multinuclearity
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: shrinkage or condensation in the size of a cell or cell nucleus (nucleus disappears)
• pyknosis
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▪ less delivery of oxygen and nutrient transport thus cause weakness and headaches
Anemia
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▪ treatment: transfusion of red cell concentrates (red cell transfusion)
Anemia
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subject to infections; sign of bone marrow failure
Neutropenia
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exhibits dysmyelopoiesis
Neutropenia
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dysmyelopoiesis characterized by:
Pseudo-Pelger-Huet, Auer rods, N:C ratio asynchrony
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: abnormal nuclear condition of WBC (hypersegmentation)
• Pseudo-Pelger-Huet
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: fused primary granules
• presence of Auer rods
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- asynchronous maturation of nucleus and cytoplasm
N:C ratio asynchrony
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- (normal) as the cell ages: ↓ cytoplasm size, segmentation of nucleus
N:C ratio asynchrony
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- cytoplasmic size ↓ without nuclear segmentation or lobulation
N:C ratio asynchrony
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- nuclear hypersegmentation (mature) with large cytoplasmic size (immature)
N:C ratio asynchrony
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treatment: transfusion of granulocyte concentrates (granulocyte transfusion)
Neutropenia
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▪ involves platelet and coagulation factors
Thrombocytopenia:
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: low platelet count
▪ bleeding
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: liver and other organs are affected as bm fail = coag factor defects and qualitative plt abnormalities
▪ clotting problems
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treatment: transfusion of platelet concentrates (platelet transfusion)
Thrombocytopenia:
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dysmegakaryopoiesis
Thrombocytopenia:
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dysmegakaryopoiesis characterized by:
• giant platelet
• hypolobulation/hyperlobulation of megakaryocytes
• micromegakaryocyte (product)
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(normal) man nucleus to signify maturation
Abnormal: hypolobulation (N:C ratio asynchrony)
hypolobulation/hyperlobulation of megakaryocytes
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▪ elevated resting energy expenditure accompanied by extreme weight loss (thin leukemic patients)
Hypermetabolism
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▪ ↓nutrient intake, ↑metabolism = nutrients are immediately metabolized (not absorbed) in ≤1 hr instead of 2 hrs (normal)
Hypermetabolism
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▪due to bone marrow failure
Organ Failure
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• treated by:
- radiotherapy or chemotherapy (Steininger)
- bone marrow transplant: least recommended due to many complications (allogeneic transplant) such as Graft versus host disease (GVHD)
Organ Failure
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CLASSIFICATIONS OF LEUKEMIAS Criteria
I. Cell Line
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I. Cell Line
1. Myeloid/Myelocytic/Myelogenous Leukemia/ Non-Lymphocytic Leukemia
2. Lymphoid/Lymphocytic/Lymphogenous Leukemia/Lymphoblastic
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II. % of Blasts in the PB and BM
1. Acute Leukemia
2. Chronic Leukemia
3. Sub-acute Leukemia
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III. Number of WBCs in the peripheral blood
1. Leukemic Leukemia
2. Sub-leukemic Leukemia
3. Aleukemic Leukemia
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1. Myeloid/Myelocytic/Myelogenous Leukemia/ Non-Lymphocytic Leukemia ▪ affected cells:
RBCs, BEN, monocytes, platelets (except lymphocyte)
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2. Lymphoid/Lymphocytic/Lymphogenous Leukemia/Lymphoblastic ▪ affected cells:
lymphocyte
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▪ with increased blast cells in the bone marrow and peripheral blood
1. Acute Leukemia
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• FAB criteria: > 30% bone marrow blasts
1. Acute Leukemia
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• WHO criteria: ≥ 20% bone marrow blasts
1. Acute Leukemia
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▪ Prognosis: rapidly progressive, with a shorter prognosis (poor) of days to 6 months
1. Acute Leukemia
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▪ < 10% blasts in PB
2. Chronic Leukemia
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▪ with better and longer prognosis (slower progression and proliferation; not responsive to treatment)
2. Chronic Leukemia
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▪ transitional stage between acute to chronic
3. Sub-acute Leukemia
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▪ 10-30 % blast in the PB plus other symptoms
3. Sub-acute Leukemia
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▪ Prognosis: at least 2-6 months
3. Sub-acute Leukemia
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:▪ WBC count: more than 15, 000/uL
1. Leukemic Leukemia
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▪ WBC count: less than 15, 000/uL
2. Sub-leukemic Leukemia
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▪ presence of immature or abnormal cells in the PB
2. Sub-leukemic Leukemia
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▪ WBC count: less than 15, 000 /uL
3. Aleukemic Leukemia
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▪ no immature nor abnormal cells in the PB
3. Aleukemic Leukemia
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FAB basis in classification of leukemia:
morphological appearance of cells in a Romanowsky stain
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1. AML/ANLL =
M1, M2, M3, M4, M5, M6, M7 (myeloid)
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2. ALL =
L1, L2, L3 (lympoid)
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WHO basis in classification of leukemia:
▪ morphology
▪ cytochemical stain
▪ immunologic markers/probes (antibodies produced): cluster of differentiation (CD)
▪ cytogenetics: chromosomal markers of leukemic cells
