Chronic Lymphoproliferative Disorders

Question 1

WHO classification of lymphoid malignancies

Answer 1

3 major groups
B-cell neoplasms
T and NK cell neoplasms
Hodgkin’s lymphoma

Question 2

CLPDs

Answer 2

Chronic lymphoproliferative disorders
Lymphomas arise from single abnormal lymphocyte
Genetic genes -> accumulation of cells-> every one of which has arisen from a a single cell (clonal expansion)

Question 3

Composition of T cell antigen receptor

Answer 3

T cell antigen receptor is composed of two chains (alpha/beta and gamma/delta)
IgG and TCRs => antigen receptors

Question 4

Antigen independent B-cell development

Answer 4

In bone marrow Pro-B-cell -> Pre-B-cell which expresses Ig
Rearrangement of heavy and light chains that code for Ig receptor

B cell encounters antigens => lymphocyte dies by apoptosis or undergoes receptor editing => high affinity molecule

Surviving B cells -> spleen, LN, or MALT for further development

Question 5

Antigen dependent B cell development

Answer 5

Secondary lymphoid organs (germinal centre)
Follicular DC present antigen to B-cells
If B cells recognise antigen =>rescued from death by T cells
Two molecular events
- somatic hypermutation
- class switching recombination

Question 6

Somatic hypermutation

Answer 6

Radom mutations acquired by B cells that change their structure improving antigen specificity
In germinal centres of LN
Affinity maturation

Question 7

Class switch recombination

Answer 7

Changes class of Ig expressed by the cell
Broadens ability of the immune system to destroy the intruder

Question 8

Where does T cell maturation occur?

Answer 8

Primary lymphoid organ (thymus)

Question 9

Gene rearrangements commonly used in CLPD diagnostics

Answer 9

[1] physiological - normal assembly of segments in AR genes in B and T cells
[2] pathological - movement of genes that are normally separated in nature

Question 10

Analysis of IGHV genes in CLL

Answer 10

B-CLL most common leukaemia in CLL
Prognostic prediction

Analysis of IGHV genes sratifies patients into two groups independent of other markers
Unmutated IGHV=more aggressive CLL
Mutated IGHV=indolent

IGHV, are not capable of triggering apoptosis, survival or proliferation due to their reduced ability to bind antigen because of their BCR (altered by SHM)

Question 11

Prognostic prediction in CLL mutations in order of increasing diversity

Answer 11

13q14 deletion
Trisomy 12q13
11q22-23 deletion
17p13 deletion/insertion

Question 12

DLBCL

Answer 12

Most common subtype of non-hodgkins lymphoma in adults
Malignant proliferation of large lymphoid cells with prominent nuclei
Collection of disease

Question 13

Gene expression profiling in DLBCL

Answer 13

3 histologically indistinguishable molecular subtypes

[1] activate B-cell like DCBCL (ABC) activated NFkB pathway
[2] germinal centre B-cell like DCBCL (GCB)
[3] primary mediastinal B-cell lymphoma (PMBC)

Question 14

4x CLPDs

Answer 14

NHL
MM
CLL
HD

Question 15

Pre-disposition to leukaemia

Answer 15

Inherited factors - familial incidence
Environmental - chemical, drugs and radiation
Infection - viruses and bacteria

Question 16

CLL

Answer 16

Chronic lymphocytic leukaemia
Most common leukaemia in UK
Majority occur later in life
Considered a subtype of Non-Hodgkin’s lymphoma
Massive overproduction of B cells -> mutated and non-functioning B cells crowd any B cells that are left
Or can affect T cells

Question 17

What test can be used to determine pattern of clonality within lymphoid infiltrate?

Answer 17

PCR for IGH chain gene (&TCR gene) rearrangement