Term
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Definition
- malignant proliferation of one or more elements of hematopoietic system, characterized by:
- primary involvement of bone marrow
- usually (but not always) circulation of neoplastic cells in the peripheral blood
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Term
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Definition
- neoplastic monoclonal proliferation of hematopoietic progenitor cells (acute) or their progeny (chronic)
- leukemic clone characteristics include:
- increased proliferation as a result of:
- inability to differentiate and mature (acute)
- increased mitosis (acute and chronic)
- increased survival of progeny (chronic)
- inhibition of normal hematopoietic clones (acute and chronic)
- leads to
- overabundance of leukemia cells (blasts or mature cells)
- deficiency of normal hematopoietic cells
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Term
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Definition
- hereditary factors (esp. DNA instability syndromes like Fanconi's anemia, Bloom's syndrome, ataxia telangiectasia)
- chemical exposure
- occupational- benzene, benzene derivatives
- therapeutic- alkylating agents, chloramphenicol, phenylbutazone
- ionizing radiation (single large dose or chronic small doses)
- chromosome/genetic abnormalities
- congenital (Down's syndrome)
- acquired- Philadelphia chromosome in CML
- viruses
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Term
| genetics defects in leukemia |
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Definition
- modifcation and/or inappropriate activation of oncogenes and/or inactivation of tumor suppressor genes
- affected oncogenes usually encode for hematopoietic cell
- GF
- GF receptor
- growth signal transducers A (esp. Tyr kinase)
- DNA TF's
- examples
- BCR-ABL affect Tyr kinase (CML)
- PML-RARA affect surface recptor that in turn affects TF's (AML)
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Term
| leukemia clinical features (differentiate chronic from acute) |
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Definition
- age- increase with age (except ALL where incidence peak at childhood and late adulthood)
- gender- slight male predominance
- acute
- abrupt onset
- rapid progression
- immature cells
- usual short survival (median survival 2-3 yrs)
- except childhood ALL (80-90% cured)
- chronic
- slow, insidious onset
- slow, but usually relentless, progression
- mature cells
- long survival (most usually die of leukemia)
- tx: bone marrow, stem cell transplant
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Term
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Definition
- peripheral blood
- anemia, neutropenia, thrombocytopenia
- circulating leukemic cells (usually)
- coagulation abnormalities (DIC)
- increased LDH, uric acid
- bone marrow
- partial to complete replacement by leukemic cells, with deficiency of normal cells
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Term
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Definition
- pallor
- petachiae or purpura
- bone tenderness
- hepatosplenomegaly
- lymphadenopathy
- gingival infiltrate
- skin lesions
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Term
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Definition
- acute
- myelogenous
- lymphoblastic
- chronic
- myeloproliferative
- lymphocytic
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Term
| subtypes of chronic myeloproliferative neoplasms |
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Definition
- chronic myelogenous leukemia
- polycythemia vera
- primary myelofibrosis
- essential thrombocythemia
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Term
| most common leukemias in US |
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Definition
- chronic lymphoblastic (MOST)
- acute myelogenous
- chronic myeloprolif.
- acute lymphoblastic (least)
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Term
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Definition
- decreased normal blood cells
- anemia (weakness, fatigue)
- neutropenia (infection and fever)
- thrombocytopenia (bleeding)
- leukemic cell infiltration
- bone pain
- abdominal discomfort
- headache
- lymphadenopathy
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Term
| WHO classification of AML |
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Definition
- AML w/ recurrent genetic abnormailities
- AML with myelodysplasia related changes
- therapy related AML
- AML not otherwise char.
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Term
| WHO classification of ALL |
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Definition
- B lymphoblastic leukemia
- with recurrent genetic abnormalities
- not othersiwe categorized
- T lymphoblastic leukemia
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Term
| acute leukemia lab evaluation that must be done |
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Definition
- morphology (see "blasts")
- high N:C ratio
- fine evenly distributed chromatin pattern
- prominent nucleoli
- inclusions in cytoplasm (ex: Auer rods = myeloblasts of AML)
- cytochemical analysis (myeloperoxidase stain)
- immunophenotypic analysis (detect Ag's on surface of cells and determine lineage/ maturation)
- cytogenetic (karyotypic) analysis (can have prognositc significance)
- DNA (genotypic) analysis (signal on cell or fluorescent tags)
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Term
| Common characteristics of chronic myeloprolif. neoplasms |
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Definition
- myelogenous/pluripotent stem cell defects resulting in overproduction of mostly mature cells
- three major non lymphocytic lineages affected, but one predominantes
- some clinical/morphologic overlap between subtypes, especially in early stages
- some subtypes share common gene abnormality
- JAK2 mutation
- affect Tyr kinase activity
- CML associated with BCR/ABL1
- transformation to acute leukemia
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Term
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Definition
- stem cell defect inducing overabundance of granulocytes (predominantly) through:
- increased granulocyte proliferation
- premature release of granulocytes from the marrow into the peripheral blood (ex: spleen)
- prolonged granulocyte lifespan (via inhibition of apoptosis)
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Term
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Definition
- slow insideous onset
- general leukemic symptoms esp. abdominal discomfort due to splenomegally
- signs
- pallor
- petechiae
- hepatosplenomegaly
- bone (esp. sternal)
- tenderness)
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Term
| CML: peripheral blood findings |
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Definition
- granulocytosis with all stages of maturation present
- anemia
- thrombocytopenia
- increase LDH, uric acid, vit B12
- LAP score decrease
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Term
| Describe leukocyte alkaline phosphatase score (LAP) (normal, when increase and decrease) |
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Definition
- 100 peripheral blood neutrophiles scored 0-4+ for amount of alkaline phosphatase
- normal (13-130)
- decrease in CML
- nomral to increase in:
- leukemoid rxn
- polycythemia vera
- primary myelofibrosis
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Term
| bone marrow findings of CML |
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Definition
- hypercellular
- marked increased neutrophiliic precursors with progressive maturation
- increase eosinophils and basophlis
- sometimes increase megakaryocytes
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Term
| Effect of BCR ABL rearrangement and pharmacological application |
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Definition
- results in abnormal Tyr kinase, but basis of tx with Gleevac and second generation tyr kinase inhibitors
- present in ALL hematopoitic lines
- IDed in all cases of true CML
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Term
| CML: acute blast transformation (crisis) |
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Definition
- imminent if unsuccessful tx, occurs in nearly all cases within 1-4 yrs
- often preceeded by accelerated phase
- definition: more than 20% of blasts in peripheral blood in bone marrow (lost ability to mature)
- myelogenous in 70% of cases and lymphoblastic in 30%
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Term
| polycythemia vera (definition, lab features) |
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Definition
- definition- stem cell defect resulting from autonomous (no EPO needed) erythrocytic cell line with some overprod. of other hematopoietic cells
- lab dx
- peripheral blood
- increase RBC mass (increase Hct)
- decrease serum EPO
- bone marrow- pancellular hematopoietic increases
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Term
| clinical features: polycythemia vera |
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Definition
- symptoms- hyperviscosity syndrome
- signs- ruddy cyanosis (dark reddish purple color to the skin), hepatosplenomegaly
- course
- thromboembolism
- hemorrhage (platelets dont work)
- myelofibrosis (burnt out stage)
- acute leukemia (AML) in 5-15% of time
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Term
| secondary polycythemia (definition, cause) |
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Definition
- definition- non neoplastic erythrocytosis secondary to physiologic or abnormal overproduction of EPO
- causes
- high altitude
- cardiopulm. disease
- alveolar hypovent ("Pickwickian syndrome")
- neoplasms (ex: renal cell or hepatocellular carcinoma)
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Term
| primary myelofibrosis (definition, pathogenesis) |
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Definition
- definition- stem cell defect inducting increased hematopoietic (esp. abnormal megakaryocytic) proliferation
- pathogenesis
- abnormal megakarycotes produce growth factors (PDGF, TGF beta)
- stimulates fibroblasts and osteoblasts
- cause marrow fibrosis, results in extramedullary hematopoiesis
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