Unit 2: Acute lymphoid leukemia Flashcards
What are the normal stages of white blood cell development?
Haematopoietic stem cell
Lymphoid precursor cell - lymphoblast (B cell and T cell), NK cells
Myeloid precursor cell
1) myeloblast
- monocyte, macrophage
- erythroblast erthyrocyte
- granulocytes ( neutrophil, eosinophil, basophil)
2) megakaryocyte then a thrombocyte to a platelet
3) mast cell
What is iron deficiency anemia?
Reduced iron levels in the blood, results in low levels of saturated Hb.
Low levels of oxygen transport in the blood.
What are the biological consequences of a t(9,22) translocation mutation in ALL?
Bcr-Abl mutation
Abl gene is under the Bcr promotor, results in an increased rate of transcription, gain of function mutation.
Transissions from a protooncogene to an oncogene
As a tyrosine kinase enyzme, increase phosphorlyation of Ras, resulting in proiferative signalling.
Known as the philadelphia chromosome.
Found in 5% of childhood ALL cases and 20-30% of adult ALL cases
What is ALL?
Acute lymphoid leukemia
Rapid onset, proliferation of lymphocytes often remain as undifferentiated lymphoblasts
Diagnosed when >20% bm is lymphoblasts or wbc count is over 50x10^9L
Reduces production of other blood cells.
What are the different types of leukemia?
Acute/chronic - rate of progression
Myeloid/ lymphoid - the cell lineage affected
What types of leukemia are common in children?
ALL is the most common in children - 1/3 of childhood cancers
Followed by AML
Chronic leukemias are rare in children.
Mechanism of action of dexamethasone
Anti-inflammatory
Steroid - cross phospholipid bilayer in membrane
Glucocorticoid receptor in cytoplams
Together move to nucleus to act as tf
Binds to glucorticoid response element
Result in change in gene expression
- decrease pro-inflam cytokines, increase anti-inflam cytokines, apoptosis of lymphocytes by reduces NFkb signalling and decreases vascular permeability.
Mechanism of action of vincristine
Binds to tubulin b, prevents from dimersing with tubulin alpha.
Inhibits microtubules formation
Spindle appartus does not form
Inhibits mitosis at metaphase
Mechanism of action of asparaginase
Converts asparagine in ECF to aspartic acid and ammonina
Tumour cell do not have an asparagine synthase enzyme, self cell do
Tumour cell unable to source asparagine from ECF, inhibits DNA formation hence inhibits mitosis,
Mechanism of action of methotrexate
Anti-folate
Inhibits dihydrofolate reductase enzyme, prevents DHF being reduced to THF.
Inhibits thmidiate synthase.
Inhibits AICART production, levels of AICAR increase which has anti-inflammatory effects
This inhibits purine, thymine, DNA and RNA synthesis
Cidal activity
Mechanism of action of mercaptopurine
Prodrug converted to TIMP this inhibits IMP so purine bases are not produced.
TdGTP - incorporated into DNA prevents elongation
TGTP - incorporated into RNA prevent elongation
Decreases NFkb signalling causing apoptosis of t-lymphocytes
Why does induction chemotherapy cause hair loss and sickness?
Chemical trigger zone in brain - activated by chemotherapy chemicals in bloodstream/CSF, activates nearby vomiting centre. Damages enteroendocrine cell causing to release serotonin which binds to the vagus nerve
Hair loss - rapidly dividing cells are preferentially targeted by chemotherapy drugs, hair follicles will be affected, so no proliferation
What are the biological mechanisms associated with ALL replase?
Reduces to undetectable amount - continue to mutate and grow if maintenance therapy is not taken, or unsuccessful in the case of resistance.
Undetected metastasis
Familial case - second hit hypothesis
What are the symptoms of anaemia?
Tiredness
Paleness
Short of breath
Heart palpitations
Cold extremities
Headaches
How can a FBC diagnose anemia, liver damage and kidney damage?
Anemia - red blood cell count, Hb levels, oxygen saturation, haemotcrit, blood smear to look at shape and size (megaerthrocyte or sickle cell)
Liver - bilirubin levels (high), albumin (low)
Kidney - albumin (high), creatine kinase (high)
