introduction to Leukaemia

Question 1

define leukaemia

Answer 1

malignant disorders of haematopoietic stem cells associated with increased number of WBC in bone marorw/peripheral blood

Question 2

what are haematopoietic stem cells

Answer 2

multipotent
self maintaining = stem cells can divide to produce more stem cells
can give risk to progenitor cells

Question 3

describe progenitor cells

Answer 3

divide to form mature cells, cannot divide inherently, eventually differentiate and mature

Question 4

describe 2 types of progenitor cells

Answer 4

1. undifferentiated progenitor cells = cant tell difference between them morphologically as they dont show characteristics of mature cells
2. committed progenitor cells = unipotent, committed as to what they’d become and when they generate mature cells

Question 5

describe incidence of leukaemia

Answer 5

related to age, higher in older people
4/10 new cases per year 75+
higher in males

Question 6

describe presentation of leukaemia

Answer 6

abnormal bruising
repeating abnormal infection
sometimes anaemia

Question 7

diagnosis of leukaemia

Answer 7

extract biopsy from bone marrow, from pelvic bone, compared with PB
peripheral blood blast test = check for presence of blasts and cytopenia
lumbar puncture = determines if leukaemia has spread to cerebral spinal fluid

Question 8

describe other diagnosis methods

Answer 8

cytomorphology 
immunophenotyping 
next gen sequencing 
flow cytometery 
fluorescence insitu hybridisation

Question 9

aetiology of leukaemia

Answer 9

exact cause unclear

combo of predisposing factors = lifestyle/genetic risk

Question 10

describe genetic risk factors

Answer 10

not usually hereditary
gene mutations involving oncogenes or activation of tumour suppressors
chromosome abberrations e.g. translocations
inherited immune system problems

Question 11

environmental risk factors

Answer 11

radiation exposure
exposure to chemicals and chemotherapy
immune system suppression

Question 12

lifestyle related risk factors

Answer 12

smoking/drinking 
exposure to electromagnetic fields 
infections early in life 
mothers age when child is born 
nuclear power station

Question 13

difference between lymphoid vs myeloid leukaemia

Answer 13

acute and chronic

Question 14

describe acute disease

Answer 14

rapid onset and short but severe cause

acute leukaemia

• undifferentiated
• uncontrolled clonal and accumulation of immature WBC

Question 15

describe chronic disease

Answer 15

persisting over a long time
differentiated
uncontrolled clonal and accumulation of mature WBC

Question 16

type of acute leukaemia

Answer 16

acute lymphoblastic and myeloblastic

Question 17

type of chronic leukaemia

Answer 17

chronic lymphocytic and granulocytic

Question 18

acute leukaemia in depth

Answer 18

characterised by large number of lymphoblasts or myeloidblasts in bone marrow = undifferentiated

symptoms:
thrombocytopenia = bruising, nosebleed, bleeding from gums
neutropenia = recurrent infections/fever
anaemia

Question 19

describe acute lymphoblastic leukaemia

Answer 19

commonest cancer of childhood 
cancer of immature lymphocytes 
b cell and t cell leukaemia 
treatment = chemotherapy 
1/10 patients relapse

Question 20

describe acute myeloblastic leukaemia

Answer 20

70 children under 16 diagnose per year
cancer of immature myeloid WBC
based of FBA system
chemotherapy, monoclonal antibodies, allogeneic bone marrow transplant therapy
results in 5 year event-free survival of 50-60%

Question 21

chronic leukaemia in depth

Answer 21

increased no. of differentiated cells
originates from large number of mature lymphocytes in bone marrow and peripheral blood
symptoms = recurrent infections, anaemia, thrombocytopenia, lymph node enlargement
chemotherapy treatment

Question 22

describe chronic myeloid leukaemia

Answer 22

large number of mature myeloid wbc
asymptomatic and discovered via routine blood tests
diagnosis = high WBC count in blood and bone marrow, philadelphia chromosome present
imatinin therapy treatment

Question 23

describe BCR-ABL oncogene

Answer 23

95% of cases of cml = have detectable philadelphia chromsome
balanced translocation of t(9;22) and q(32;q11) = causes philadelphia chromosome
BCR = encodes protein that needs to be constantly active
ABL = encodes protein tyrosine kinase whose activity is tightly regulated
BCR-ABL. = constitutive protein tyrosine kinase activity

Question 24

unregulated BCR-ABL causes

Answer 24

proliferation of progenitor cells in absence of growth factors
decreased apoptosis
decreased adhesion to bone marrow stroma
95% of CML cases have phi chromosome

Question 25

therapy

Answer 25

imatinib = small molecule inhibitor targetting Abl-CML treatment
remission induced in more patient, greater diversity and fewer side effects
some patients drug resistant