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