Leukaemia And Lymphoma

Question 1

What cells are all blood cells derived from

Answer 1

Multipotential haemopoitetic stem cells

Question 2

What 2 cells do mutlipotential haemopoietic stem cells differenitate into

Answer 2

Common myeloid progenitor

Common lymphoid progenitor

Question 3

What cells does myeloid progenitor cells give

Answer 3

Granulocytes

Red blood cells

Question 4

What cells do lymphoid progenitor cells give rise to

Answer 4

Natural killer cells

Lymphocytes; t and b

Question 5

What does leukemia arise from

Answer 5

Haemopoitetic stemm cells

Question 6

What happens to the bone marrow when normal haemopoeisis is impaired

Answer 6

The bone marrow produces abnromal blood cells which leads to bone marrow failure

Question 7

What happens when the bone marrow fails

Answer 7

You become:
anaemic
Prone to bleeding and bruising
Suspectible to infection

Question 8

What are the 4 types of leukemia

Answer 8

Acute myeloid leukemia
Acute lymphoid leukemia
Chronic myeloid leukemia
Chronic lymphoid leukemia

Question 9

What is the difference between chronic and acute leukemia

Answer 9

Acute leukemia involve the transformation of immature haemopoetic cells
Chronic leukemia invlve the cells that done further differentiation i.e are more mature cells

Question 10

In chronic leukemia what can the accumulaton of cells lead to

Answer 10

Splenomegaly
Hepatomegaly
Lymphadenopathy

Question 11

What is lymphoma

Answer 11

Cancer of the lymphoid tissue

Question 12

What are the 2 main categories of lymphoma

Answer 12

Non hodgkin

Hodgkin lymphoma

Question 13

What is lymphoma characterised by

Answer 13

Proliferation and accumulation of mature lymphocytes in lymphoid tissue resulting in lymphadenopathy and or hepatosplenomegaly

Question 14

What are the b symptoms in lymphoma

Answer 14

Night sweats
Intense prutitus
Unexplained fever
Unintentional weight loss
Fatigue and generalised weakness

Question 15

What investigations should you carry out in suspected blood cancer

Answer 15

FBC
UE, lft, CRP and calcium
Coagulation profile (PT,APTT, fibrinogen)
Blood culture and screening for infection
Blood film
Peripheral blood immunophenotyping
Diagnoistic bone marrow aspirate and trephine biopsy

Question 16

If you suspect lymphom what investigations should you carry out

Answer 16

LDH
Lymph node biopsy and history
CT imaging and PET scan

Question 17

What is acute promyelocytic leukemia

Answer 17

A subset of acute myeloid leukaemia

Question 18

For myleoid progenitor cells to give rise to granulocytes what does it need to differnitate to

Answer 18

Myeloblast

Question 19

What do myeloblast cells differnitate into to give neutrophils

Answer 19

Promyelocyte
Myelocyte
Metamyelocyte
Band cell
Neutrophil

Question 20

In acute prmyelocyte leukemia what happens to the differentiation

Answer 20

There is a block to promyelocyte so no further differentiation occurs and you seen no neutrophils on the blood film

Question 21

What is the distinct molecular abnormality that underpins acute promyelocytic leukemia

Answer 21

Recipricol translocation between chromosome 15 and 17

Question 22

When recipricol translocation occur which gene forms

Answer 22

PML-RARA on chromosome 15 and RARA-PML on chromosome 17

Question 23

When PML-RARA gene is translated what protein does it form

Answer 23

PML-RARA protein

Question 24

What is the role of PML-RARA protein

Answer 24

Block the promyelocyte differentiation

Question 25

What is the treatment of acute promyelocytic leukemia

Answer 25

Vitamin a derivate i.e all trans retinoic acid given with arsenic trioxide (ATRA)

Question 26

What are the other treatment for other types of acute myeloid leukemia

Answer 26

Chemotherapy Monoclonal antibody Allogenic stem cell transplantation

Question 27

What is chronic myeloid leukemia due to

Answer 27

Recipricol translocation of chromsome 9 and 22 that foms BCR-ABL gene

Question 28

What is the specific treatment of chronic myeloid leukemia

Answer 28

Tyrosine kinase inhibitor to stop the fusion of bcr and abl gene e.g imatinib

Question 29

What is a problem of using imaitib

Answer 29

The patient can develop imatinib resistance

Question 30

How do we solve imatinib resistance

Answer 30

Using 2 and 3rd generation tyrosine kinase inhibitors

Question 31

What are the features of CML on a blood film

Answer 31

Few rbc and platelets Many white blood cells Eosinophil precursors

Question 32

What is chronic lymphocytic leukemia characterised by

Answer 32

Accumulation of mature b lymphocytes

Question 33

What is the pathobiology of chronic lymphocytic leukemia

Answer 33

B cell receptors drive CLL proliferation and CLL cells express BCL-2 (anti-apoptotic protein) which makes them resistant to apoptosis

Question 34

What is the treatment of CLL

Answer 34

``` Chemotherapy Monoclononal antibodies e.g rituximab Chemoimmunotherapy BCR signalling inhibitors e.g ibrutinib BCL2 inhibitor e.g venetoclax ```

Question 35

What are the symptoms of hodgkin lymphoma

Answer 35

B symptoms Lymphadenopathy Mediastinal lymph node mass

Question 36

What is the treatment of Hodgkin’s lymphoma

Answer 36

Chemotherapy and radiotherapy Monoclonal antibody e.g brentuximab Immune checkpint PD1 inhibitor Autologous stem cell transplatantion

Question 37

What is a feature of hodgkins lymphoma and histology

Answer 37

Sternbers cell (owle eye cells)

Question 38

In hodgkin lymphoma what is the role of PD1

Answer 38

1. EBV Infection or JAK/STAT activation mediate the expression of PDL1 on the cell surface of reenberg cells 2. PDL1 interacts with PD1 receptors on t cells which causes on inhibitory signal to prevent t cells from destroying it

Question 39

What is the action of PD1 inhibitors in the treatment of hodgkin lymphoma

Answer 39

1. PD1 inhibitors block the interaction of PDL1 on the reenberg cell 2. This promotes t cell killing

Question 40

What receptor does sternbeg cell express on the surface

Answer 40

Cd30

Question 41

What is the mechanism of action of brenutixumab

Answer 41

Binds to CD30 and become internalised into the sternberg cell The antibody i.e brunitixumab releases toxin to kill the cell

Question 42

What is a common type of non-hodgkin lymphoma

Answer 42

Large b cell lymphoma

Question 43

What does immunohistochemistry for b cell lymphoma show

Answer 43

Positive cd20 Negative cd3 Overepxressed bcl6

Question 44

What is the treatment of large b cell lymphoma

Answer 44

Cd20 monoclonal antibodt e.g retuximab | CAR T cell therapy

Question 45

What is CAR T cell therapy

Answer 45

You collect t cell from the patient T cell is engineered with an artificial t cell receptor that recognise cd19 on lymphoma cells CAR T cell exert cytotoxic activity by interacting with C19 and killing the lymphoma