Leukaemia

Question 1

Explain the concept of leukaemia

Answer 1

malignant disorders in leukocyte synthesis = associated with increase in WBC in bone marrow and peripheral blood
clonal disease with genetic mutations can be pinned from singular cell with permenant division and avoid programmed cell death.

Question 2

Identify and discriminate the different types of leukaemia.

Answer 2

ACUTE:
accumulation of lymphoblast and myoblasts (immature cells) difficult to differentiate
(acute lymphoid, acute myeloid [blastic] )
mainly children, sudden/early onset, short duration, high BLAST cells
lack of balance between cell proliferation v. cell maturation and cell death (thrombocytopenia, purpura bleeding, bruising in gums)
nuetropenia = recurrent infections / anaemia = shortness of breath

CHRONIC:
cells have differentiated
classified by increased UNCONTROLLED clonal accumulation of mature WBC
(chronic lymphoid, granulocytic [cytic] )
later onset, increased mature blood cells, insidious onset, long duration

Question 3

Discuss the main molecular mechanisms and genetic alterations underlying the disease.

Answer 3

tumour suppressor gene suppression
imbalance between cell proliferation and cell maturation and cell death

Question 4

Describe the molecular basis of Imatinib therapy for BCR+ABL -CML.

Answer 4

BCR-ABL (chromosome 9 & 22) fusion of BCR and ABL chromosome aberration
BCR: strong promoter region, normally for protein function which is continually active
ABL: auto-inhibited protein tyrosine kinase (requires ATP for substrate phosphorylation)
= increased protein tyrosine kinase activity = increased proliferation of progenitors even without growth factors, decreased apoptosis & decreased bone cell stroma adhesion.

IMATINIB =
competes with ATP binding to BCR-ABL+ subsrate which reduced phosphorylation = fusion oncogene protein cannot activate downstream pathways
some patients become drug resistant => gastrointestinal stromal tumours