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pathophysiol-ogy of leukaemia
pathophysiolo-gy of leukaemia
genetic changes associated with blood cancers
treating cancer
treating cancer
100

what is leukaemia

a group of conditions characterised by an increase in premature leukocytes, which are released into the bloodstream

100

examples of types of leukaemia

acute myeloid leukaemias, acute lymphocytic leukaemias, chronic myeloid leukaemias and chronic lymphocytic leukaemias

100

how many alleles must be mutated to convert a proto-oncogene into an oncogene

one 

100

what is neoadjuvant therapy?

radio/ chemotherapy given before elective surgery to attempt to shrink tumours which are primarily unresectable

100

what is adjuvant therapy?

chemo/ radiotherapy given after surgery reducing the risk of relapses and metastases

200

symptoms of acute leukaemias 

  • anaemia, epitaxis, bleeding gums, petechiae, fever and frequent infections, hepatosplenomegaly 
  • usually develop over a 4-6wk period
200

difference between childhood and adult acute leukaemias 

acute childhood leukaemias are more commonly lymphoblastic whereas acute adult leukaemias are more likely to be myelogenous 

childhood leukaemias are more likely to be acute than chronic 

200

what is the Philadelphia translocation 

translocation of a portion of chromosome 9 onto chromosome 22, producing the BCR-ABL protein and up-regulating tyrosine kinase activity predisposes particularly to chronic myeloid leukaemia

200

common side effects during chemotherapy 

pancytopenia, alopecia, stomatitis (mouth/ lip inflammation), mucositis, nausea, vomiting

200

examples of anti-neoplastic therapy

  • surgery
  • chemotherapeutic drugs
  • radiotherapy 
  • targeted therapy 
300

describe the process of erythropoiesis 

haematopoietic stem cell to common myeloid progenitor to erythroblast to reticulocyte before maturing into a RBC

300

features of chronic phase of CML 

  • persists up to 10 yrs 
  • weight loss, fever, night sweats and fatigue 
  • LUQ pain due to splenomegaly 
  • how does CML present during the accelerated phase?
  • anaemia, infections and fever 
  • infarctions (due to pleocytosis), leukaemic priapism, myelofibrosis 
  • extreme splenomegaly
300

example of a tumour suppressor gene 

  • TP53 (most cancers)
  • Rb (retinoblastoma and osteosarcoma)
  • APC gene (codes for protein that prevents unregulated cell division by inhibiting B-catenin synthesis, implicated in some colorectal cancers)
300

how does radiotherapy work?

  • radiation interacts with oxygen to produce free radicals which damage DNA 
  • DNA damage cannot be repaired in malignant cells as well as in normal cells
  • therefore malignant cells cannot regenerate whereas normal cells can 
300

how can tumours develop resistance to cancer drugs 

subclones can emerge from the heterogenous tumour and secondary mutations may occur to confer resistance

400

investigations for acute leukaemia 

  • full blood count showing low platelet or RBC counts 
  • presence of myeoblasts and lymphoblasts in a peripheral blood smear 
  • bone marrow aspiration and biopsy to examine morphology, hitsochemistry, cyotgenetics and for immunophenotyping 
  • imaging and CSF analysis can be used if organ failure suspected 
400

describe the pathophysiology of CLL 

  • acquired mutations of haematopoietic stem cells causing increased proliferation of leukaemic B cells 
  • this suppresses the proliferation of normal blood cells 
  • abnormal B cells infiltrate the lymph nodes, spleen and liver
400

example of a photo-oncogene

  • BRAF (serine/ threonine kinase, associated with melanoma, NH lymphoma and thyroid carcinoma)
  • BCR-ABL (tyrosine kinase associated with CML and ALL)
  • HER2 (receptor tyrosine kinase associated with breast and gastric cancer)
  • CDK4 (cyclin dependant kinase associated with melanomas)
400

how do topoisomerase inhibitors work?

  • topoisomerase I- decrease DNA replication and cause DNA degradation by hydrolysing one strand of DNA)
  • topoisomerase II- cause DNA degradation by causing breaks in the DNA helix 
400

how do taxanes work?

  • stabilise microtubulues during mitosis to arrest cells at metaphase 
500

what is the rai staging system 

  • used to classify chronic lymphoid leukaemias based on stage, findings, risk and median survival times 
  • stage 0- isolated lymphocytosis 
  • stage I- lymphadenopathy 
  • stage II- hepatomegaly and/ or splenomegaly 
  • stage III- anaemia
  • stage IV- thrombocytopenia
500

differences between cell morphology for ALL and AML

AML- 

  • large blasts
  • round/ kidney shaped nuclei 
  • more cytoplasm
  • prominent nucleoli 
  • fine granules and auer rods (eosinophillic rods)

ALL

  • large blasts 
  • large irregular nuclei 
  • inconspicuous nucleoli 
  • coarse granules 
  • no auer rods
500

pathophysiology of CML 

  • presence of the philadelphia chromosome causes ABL1 gene to fuse with the BCR gene forming a gene coding for a non-receptor tyrosine kinase which has increased enzymatic activity
  • this inhibits physiologic apoptosis and increases the mitotic rate resulting in uncontrolled proliferation of granulocytes
  • acquisition of mutations to tumour suppressor genes over the course of the disease result in the progression from chronic to acute leukaemia
500

examples of antibiotics used as chemotherapeutics 

  • bleomycin 
  • actinomycin D
  • anthracyclines 
500

classes of anti-metabolic chemotherapeutic drugs 

  • antifolates
  • pyrimidine antagnoists 
  • purine analogues
  • ribnucleotide reductase inhibitors 
  • purine antagonists