12 B-cell lymphomas Flashcards by Evie !

1️⃣ What are lymphoid tumours?

Clonal expansions of lymphoid cells due to acquired genetic changes leading to abnormal proliferation, survival, and differentiation.

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Where can lymphoid tumours arise?

Primary lymphoid tissues (bone marrow, thymus)
Secondary lymphoid tissues (lymph nodes, spleen, MALT)
Tertiary sites (skin, GI tract, brain)
Blood

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What is the difference between lymphoma and leukaemia?

Lymphoma: Predominantly affects solid tissues.
Leukaemia: Predominantly affects blood and bone marrow.

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How can normal B-cell physiology lead to lymphoid tumours?

B-cells undergo frequent genetic rearrangements (VDJ recombination, somatic hypermutation), increasing the chance of oncogenic mutations.

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hich oncogenic viruses contribute to lymphoid tumours?

Epstein-Barr Virus (EBV)
Human T-lymphotropic virus 1 (HTLV-1)
Human Herpesvirus (HHV)

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How does immunodeficiency increase lymphoma risk?

Genetic instability
Viral susceptibility
Immune dysregulation

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Which chronic immune conditions are risk factors for lymphoma?

Autoimmune diseases
Chronic H. pylori gastritis
Coeliac disease

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What mutagenic agents contribute to lymphoid tumours?

Radiotherapy
Chemotherapy
Pesticides

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What factors define each type of lymphoid neoplasm?

Host immune system & tumour microenvironment
Somatic genetic alterations
Normal cell counterpart
Constitutional genetics

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Which is more common: B-cell or T-cell neoplasms?

B-cell lymphoma/leukaemia is more common than T-cell neoplasms.

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How does pathological subtype affect clinical outcome?

Different subtypes respond differently to treatment, affecting prognosis.

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What is used as a paradigm for studying lymphoid tumours?

B-cell lymphomas

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What are normal B-cell differentiation steps?

VDJ recombination
Somatic hypermutation
Class switch recombination

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What is the significance of B-cell maturation?

It predisposes B-cells to genetic changes that can activate proto-oncogenes.

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Which B-cell subsets are linked to neoplasms?

B-cell precursors → Lymphoblastic lymphoma
Naïve B-cell → Mantle cell lymphoma
Memory B-cell → MALT lymphoma
Plasma cell → Myeloma

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What are the two main types of DLBCL?

IGH highly mutated (CD10, BCL6, LMO2, etc.)
IGH mutated (IRF4, Cyclin D2, FOXP1, etc.)

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What are common types of somatic genetic alterations in B-cell neoplasms?

Chromosomal copy number changes
Deletions & duplications
Chromosomal translocations

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Which chromosome translocation is common in follicular lymphoma?

t(14;18) → IGH-BCL2

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Which chromosome translocation is common in Burkitt lymphoma?

IGH-MYC

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What role does AID (Activation-Induced Cytidine Deaminase) play?

It induces somatic hypermutation & class switch recombination, but also causes mutations leading to lymphoma

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What is VDJ recombination?

Rearrangement of immunoglobulin genes by RAG1/RAG2 to generate antibody diversity.

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How does VDJ recombination contribute to lymphoma?

Errors during recombination can translocate oncogenes near immunoglobulin loci.

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What does class switch recombination (CSR) do?

Changes antibody isotype (IgM → IgG, IgA, etc.).

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How does CSR contribute to lymphoma?

AID-induced double-strand breaks can cause oncogene translocations.

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hich translocations occur at IGH switch regions?

IGH-MYC → Burkitt lymphoma IGH-BCL6 → DLBCL IGH-various → Plasma cell myeloma

What are oncogenes and tumour suppressor genes (TSGs)?

Oncogenes: Promote tumour growth (gain of function). TSGs: Suppress tumour growth (loss of function).

hich oncogene is linked to follicular lymphoma?

BCL2 (anti-apoptotic)

Which oncogene is linked to mantle cell lymphoma?

Cyclin D1 (cell cycle control)

How does BCL6 contribute to DLBCL?

Blocks differentiation (Blimp1) Promotes mutagenicity (p53 suppression) Enhances proliferation (p21 suppression)

Which transcription factor is dysregulated in ABC-DLBCL?

BLIMP1

How do B-cell lymphomas escape immune detection?

Loss of antigen presentation Loss of immune cell killing

How do B-cell lymphomas inhibit the immune system?

T-cell exhaustion Increased regulatory T-cells (Tregs)

How do B-cell lymphomas modify immune responses?

Increased follicular helper T-cells (TFH) Loss of BTLA-inhibitory effect

hat are standard treatments for lymphomas?

Expectant management Localised radiotherapy Chemotherapy (single or multi-agent) Stem cell transplant

What novel targeted agents are used for B-cell lymphomas?

Small molecule inhibitors Antibody-drug conjugates Immune checkpoint inhibitors

What is CAR-T cell therapy?

Genetically modified T-cells engineered to target lymphoma cells.

Why are oncogenic lesions common in B-cells?

B-cells undergo frequent genetic recombination & hypermutation.

How does understanding B-cell biology improve lymphoma classification?

It allows for molecular subtyping and precision medicine approaches.

What is a key principle of B-cell neoplasia?

B-cell lymphomas retain properties of their normal cell counterparts.

Which viruses are linked to lymphomas?

EBV, HTLV-1, HHV.

What drives B-cell lymphoma development?

Genetic mutations, translocations, immune dysregulation.

What makes B-cells particularly prone to oncogenesis?

VDJ recombination, somatic hypermutation, class switch recombination.

What is the main treatment strategy for aggressive lymphomas?

Multi-agent chemo-immunotherapy.

Which immune checkpoint inhibitors are used in lymphoma?

PD-1 inhibitors (e.g. Nivolumab, Pembrolizumab).

What happens to BCL-2 expression during normal B-cell differentiation?

Naïve B-cell: BCL-2 OFF Germinal centre B-cell: Proliferates, undergoes somatic hypermutation, competes for antigen Survival signal received → BCL-2 ON → Differentiates into memory B-cell or plasma cell

What is somatic hypermutation (SHM)?

A process where B-cells introduce mutations in the Ig variable region to improve antigen affinity.

What is affinity maturation?

A selection process where B-cells with the highest antigen affinity survive and proliferate.

Which normal B-cell counterpart does lymphoblastic lymphoma resemble?

B-cell precursor (TdT+, slg-)

Which normal B-cell counterpart does mantle cell lymphoma resemble?

Naïve B-cell (IgD+, unmutated, CD10-/BCL6-)

Which normal B-cell counterpart does MALT lymphoma resemble?

Memory B-cell (IgD-, CD10-/BCL6-)

Which normal B-cell counterpart does multiple myeloma resemble?

Plasma cell (mutated, switched, PC Ags)

hat are common chromosomal translocations in B-cell lymphomas?

IGH-MYC → Endemic Burkitt lymphoma IGH-CCND1 → Mantle cell lymphoma IGH-BCL2 → Follicular lymphoma

ow does AID contribute to mutagenesis?

AID initiates somatic hypermutation and class switch recombination but can erroneously mutate oncogenes.

What types of mutations occur in B-cell lymphomas?

Missense mutations (single amino acid change) Nonsense mutations (premature stop codon) Insertions & deletions

What is base excision repair (BER) in AID-induced mutagenesis?

Short patch ncBER → Mutations at G:C base pairs Long patch ncBER / MMR → Mutations at A:T base pairs

How does AID lead to chromosomal translocations?

AID creates DNA double-strand breaks in the immunoglobulin (Ig) gene, which can translocate oncogenes.

How does epigenetic regulation contribute to germinal centre B-cell lymphomas?

berrant DNA methylation Histone modifications Dysregulation of chromatin remodelling genes

How do B-cell lymphomas suppress anti-tumour immune responses?

Downregulation of MHC molecules → Reduced antigen presentation Secretion of immunosuppressive cytokines (TGF-β, IL-10)

How does follicular lymphoma escape immune surveillance?

By increasing regulatory T-cells (Tregs) and impairing cytotoxic T-cell function.

How does BCL6 contribute to diffuse large B-cell lymphoma (DLBCL)?

Blocks differentiation (inhibits Blimp1) Promotes mutagenicity (inhibits p53) Enhances proliferation (inhibits p21)

Which key transcription factor is lost in ABC-DLBCL?

BLIMP1

Why are oncogenic lesions common in B-cells?

Because normal B-cell development involves high levels of genetic recombination and mutatio