Lecture 5 - Leukemia: Pathogenesis And Pathophysiology Flashcards
1
Q
Leukemia
A
- a malignant proliferation of cells that arises following mutation within a single hematopoietic cell
- infiltate bone marrow and interfere with marrow function
- usually circulate in blood
2
Q
Embryonic stem cell
A
- can create any tissue in the body
- derived from inner cell mass of early embryos
- ethicallyu ambiguous
- no specific phenotype
3
Q
Hematopoietic stem cells
A
- can create any type of blood cell and probably bone, cartilage and fat
- found principahlly in bone marrow in adulthood, can also be collected from umbilical cord blood of newborks
- can be safely harvested and without ethical concerns
- currently thought to be at the highest concentration in the CD34+ population
4
Q
Leukemia categories
- acute vs chronic
- myeloid vs lymphoid
A
- acute: likely to die within weeks if untreated but cure possible
- chronic have a much more indolent course, large number of patients dont require treatment at all
- AML, CML, ALL, CLL
5
Q
Acute leukemia etiology
A
- hereditary: don’t really run in families but associated with bloom’s syndrome, Fanconi anemia, Down’s syndrome, atacia telangiectasia, Wiskott-Aldrich syndrome
- Anteedent stem cell disorder: myeloproliferative neoplasms, nyelodysplastic syndromes, aplastic anemia, PNH
- chemicalsL benzene, organic solvents
- cytotoxic agents: alkylating agents, topoisomerase II inhibitors
- Radiation: atomic bomb, radiation therapy, electromagnetic radiation
- viruses: HTLV-1, HTLV-2
6
Q
Bone marrow trephine findings
A
- much more hypercellular, fat spaces nearly disappeared
- BM fails because taken over by leukemia
7
Q
Bone marrow aspirate findings
A
- monomorphic cells
- cells all look the same: large, big, more nucleate
- get rid of healthy hematopoietic cells
8
Q
Consequences of leukemia
A
- bone marrow failure
- infiltration by leukemic cells
- systemic effects
9
Q
Bone marrow failure syndrome
A
- failure of Haematopoietic cell function -> impaired red cell, white cell and platelet production
- many causes including: marrow infiltration by malignancy or rarely infection, bone marrow damage by immune or chemical agents, ionizing radiation
- marrow failure is common in leukemia
10
Q
Clinical consequences of bone marrow failure
A
- anemia: impaired red cell production, fatigue, pallor, dyspnoea, cardiac failure
- leucopenia: impaired granulocyte and monocyte production, lack of phagocytosis of micro-organisms, fever, infections
- thrombocytopenia: bruising, bleeding, risk of serious GIT or CNS bleeding
11
Q
Other clinical and heamatological features
A
- infiltration: leukostasis, bone pain, CNS involvement, hepatosplenomegaly, lymphadenopathy, gum hyperplasia, testes, chloroma
- metabolic effects: fever, anorexia, weight loss, disseminated intravascular coagulation, spontaneous tumour lysis - increased uric acid production -> renal failure
12
Q
Clonal theory of malignancy
A
- cancers arise from malignant transformation of a single cell
- but clonal hemapoiesis doesnt always lead to malignancy: 4% of people have clonal hemapoiesis, slightly increase risk of developing cancer but something else needs to happen
13
Q
Examples of clonal changes
A
- repeated identical chromocome abnormalities
- repeated DNA changes and mutations: gene rearrangements
- repeated protein abnormalities: aberrant immunophenotype, light chain restriction
14
Q
Some common leukemia-associated chromosomal translocation
A
- APL - RARA gene
- AML M2 - RUNX1 gene
- ALL -> MLL gene
- CML and ALL -> ABL gene (t(9;22))
- Burkitt’s lymphoma and leukemia - > MYC gene (t(8;14,2,22))
15
Q
Imatinib
A
- TK inhibitor
- sits in ATP bindign site and stop fusion protein from binding to substrate
- very effective
