13) Molecular Biology of Lymphoma

Question 1

Describe the epidemiology of haematological malignancies:

Answer 1

Often a disease diagnosed in the elderly

Diffuse large B cell lymphoma is most common of lymphomas, followed by follicluar lymphoma

Question 2

Differentiate between sporadic and endemic Burkitt’s

lymphoma:

Answer 2

Endemic (African) variant most commonly occurs in children living in malaria endemic regions of the world. Epstein-Barr virus (EBV) infection is found in nearly all patients
Sporadic lymphomas are rarely associated with the Epstein–Barr virus
Different break points for translocation

Question 3

Describe the translocation in the genesis of Burkitt’s lymphoma:

Answer 3

8;14. c-myc into heavy immunoglobulin chain locus

Question 4

What is the function of the c-myc oncogene?

Answer 4

Increases cell cycle progression and cellular growth

Question 5

Describe the translocation in the genesis of follicular lymphoma:

Answer 5

14;18

Question 6

How does bcl2 upregulation contributes to tumour development in follicular lymphoma?

Answer 6

Bcl-2 under the influence of antibody enhancer becomes constantly expressed and prevents apoptosis

Question 7

Describe the role of BCL-6 and BLIMP-1 in the development of diffuse large B cell lymphoma (DLBCL):

Answer 7

BCL-6 is hypermutated as it allows proliferation of B cells. BLIMP-1 is underexpressed as it negatively regulates BCL-6 and reduces proliferation

Question 8

Describe chromosomal imbalance in DLBCL:

Answer 8

Underexpression on chromosome 6 (BLIMP-1), overexpression at chromosome 3 (BCL-6)

Question 9

Describe the alteration in B cell receptor signalling as

identified through NGS sequencing of DLBCL:

Answer 9

Can become activated leading to NF-KB activity (cell proliferation and survival)

Question 10

Describe the translocation in mantle cell lymphoma:

Answer 10

11;14, causing overexpression of cyclin D1

Question 11

Give examples of lymphomas caused by viruses:

Answer 11

Burkitt’s - Epstein Barr Virus
Primary effusion lymphoma - HHV8
Adult T cell leaukemia lymphoma - HTLV1

Question 12

Describe the relevance of flow cytometry in the study of white cell malignancies:

Answer 12

Samples of cells are treated with antibodies that stick to certain proteins on cells and are detected by a machine.
Can help determine whether a lymph node is swollen because of lymphoma. Can also be used for immunophenotyping – determining which type of lymphoma a person has, based on certain proteins in or on the cells.

Question 13

What are some germinal centre derived lymphomas?

Answer 13

Burkitt’s, follicular, DLBCL

Question 14

Why are lymphomas often derived from germinal centres?

Answer 14

Area of intense proliferation

Enzymes (de-aminase) can cause DSB

Question 15

Describe the histological appearance of Burkitt’s lymphoma:

Answer 15

Starry sky appearance - lymphoma cells and macrophages

Large nucleus with vacuoles in cytoplasm

Question 16

How does the translocation of c-myc lead to development of Burkitt’s lymphoma?

Answer 16

Myc gene is brought under influence of antibody enhancer (always on) so myc is constantly expressed