chris pepper lecture 1

Question 1

what is the cause of leukaemia?

Answer 1

Leukaemia is blood cancer and is characterized by failure of the blood cells to differentiate into mature functional leucocytes.

Question 2

what happens in acute leukaemia?

Answer 2

• In Acute Leukaemia differentiation arrest early in haematopoiesis results in immature Leucocytes accumulating in the bone marrow.
• As they are not differentiated enough to leave the bone marrow they often accumulate here and the patients present with a low WBC or have immature leucocytes in the blood.

Question 3

what happens in chronic leukaemia?

Answer 3

In chronic leukaemia cells are more differentiated but dysfunctional.

patients have an increased WCC because they can leave the BM

Question 4

which cells does CLL affect?

Answer 4

Clonal disorder of mature CD5+/CD19+ B cells

Question 5

what is the most common leukaemia in the western world?

Answer 5

CLL

Question 6

what is the effect of CLL?

Answer 6

Immune dysfunction
Infection
Autoimmunity
splenomegaly 
BM failure

• Highly variable outcomes.
• Incurable with current treatments

Question 7

where do tumours arrise in CLL?

Answer 7

• bone marrow

- secondary lymphoid tissue

Question 8

what is the cause of bruising and anaemia in CLL?

Answer 8

• Anaemia caused by lack of space in the BM for normal red blood cell development
• Bruising again is caused by lack of space in the BM for normal platelet development.

due to the malignant clone taking up all the space and normal RBC and Platelet progenitors unable. To compete.

Question 9

what are some theories for causes of CLL?

Answer 9

• infection
• chemical exposure
• diabetes
• genetic

but we still don’t fully know

Question 10

what is the median age f incidents of CLL?

Answer 10

65-70

Question 11

how is CLL traditionally diagnosed?

Answer 11

• using matures scoring system
• 4/5 is typical of CLL
• score given based on a number of antigens expressed on B cell surface

Question 12

how is CLL diagnosed microscopically?

Answer 12

• smudge cells seen on a blood film

Question 13

what is wrong with the matures scoring system?

Answer 13

The problem with the matutes system is that it is difficult to always be sure its cll

as non-hodgkin lymphoma’s in leukaemic phase could have a similar phenotype.

Question 14

what is the new way that CLL is diagnosed?

Answer 14

• rawstron et al in 2017 used flow cytometry to look for…

Monoclonal mature B-cells
Kappa/lambda light chain
CD5+/CD19+/CD20+/CD23+
CD43, CD79b, CD81, CD200, CD10, and ROR1

Question 15

which compartments are affected in CLL?

Answer 15

1. peripheral blood
   - here they dot proliferate as much
2. lymph nodes
   - here they show much higher proliferative drive
3. bone marrow
   - here the cells are also much more resistant to chemotherapy

Question 16

where are niche hiding places for cll lymphocytes?

Answer 16

• lymphoid tissues

- bone marrow

Question 17

why are CLL B cells proliferating in lymphoid tissues?

Answer 17

• CD20 B cells are found bound to CD3 T cells in CLL patient lymph nodes
• this leads to activation of the B cell and subsequent proliferation

Question 18

what is the incidence of CLL?

Answer 18

5/100,000