WK2 - Blood Cancer

What is haematopoiesis?

The process of making all blood cells from haematopoietic stem cells (HSCs) in the bone marrow.

What are the two main lineages of haematopoiesis?

Myeloid lineage (myelopoiesis) and Lymphoid lineage (lymphopoiesis).

What cells are produced by myelopoiesis?

Red blood cells (erythrocytes), platelets (thrombocytes), neutrophils, eosinophils, basophils, and monocytes (which become macrophages).

What cells are produced by lymphopoiesis?

B cells (antibodies), T cells (cell-mediated immunity), and NK cells (natural killer cells).

Where do T cells mature?

In the thymus. (B cells mature in bone marrow).

What are the three main types of blood cancers?

Leukaemia (blood and bone marrow), Lymphoma (lymphatic system), Myeloma (plasma cells).

How is leukaemia classified?

By how quickly it progresses (acute vs chronic) and which blood cells are affected (lymphoid vs myeloid).

What is the difference between acute and chronic leukaemia?

Acute = rapid progression, many immature blast cells. Chronic = slower progression, more mature cells.

What is Chronic Myeloid Leukaemia (CML)?

A cancer of myeloid lineage caused by the Philadelphia chromosome – a translocation between chromosome 9 and 22, creating the BCR-ABL fusion gene.

What is the Philadelphia chromosome?

A translocation t(9;22) that creates the BCR-ABL fusion gene. Found in CML. BCR-ABL is a constitutively active tyrosine kinase.

What is the mechanism of BCR-ABL in CML?

BCR-ABL is a fusion protein with always-on tyrosine kinase activity. It sends constant growth signals, causing uncontrolled proliferation of myeloid cells.

What drug targets BCR-ABL in CML?

Imatinib (Gleevec) – a tyrosine kinase inhibitor that blocks BCR-ABL. It was the first cancer drug designed against a specific molecular defect.

What is the significance of Imatinib?

First targeted therapy designed against a specific molecular defect (BCR-ABL). Transformed CML from a fatal disease to a manageable chronic condition.

What is Burkitt's lymphoma?

A cancer of B cells (lymphoma). Endemic form is associated with Epstein-Barr virus (EBV) and cMYC translocation.

What is the genetic cause of Burkitt's lymphoma?

A translocation involving the cMYC gene and immunoglobulin genes (e.g., t(8;14)). This causes cMYC to be constantly active.

What is the role of EBV in Burkitt's lymphoma?

Epstein-Barr virus is found in almost 100% of endemic Burkitt's lymphoma cells. EBV may contribute to B cell proliferation before the cMYC translocation.

What are the surface markers expressed on Burkitt's lymphoma B cells?

CD10, CD19, CD20, CD22, CD79a. CD20 is the target for Rituximab.

What is Rituximab?

A monoclonal antibody that targets CD20 on B cells. Used to treat Burkitt's lymphoma and other B cell malignancies.

How does Rituximab kill cancer cells (two mechanisms)?

1) Cross-linking CD20 triggers calcium influx → caspase activation → apoptosis. 2) Fc region binds FcγR on NK cells → perforin/granzyme release → antibody-dependent cell-mediated cytotoxicity (ADCC).

What is multiple myeloma?

A cancer of plasma cells (antibody-producing cells). Malignant plasma cells produce a useless antibody called paraprotein.

What is paraprotein?

A useless antibody produced by myeloma cells. It has no function and can cause kidney damage. It is a marker for myeloma.

What is the clinical course of multiple myeloma?

Relapse-remitting. No curative treatment exists, but life can be prolonged with therapy.

What are the risk factors for multiple myeloma?

Obesity (12% higher risk per 5 unit BMI), family history (4x increased risk), and possibly farming (pesticides).

What was the first patient treated with nitrogen mustard?

A patient with lymphosarcoma. Tumours shrank within days, but the patient died from leukopenia (low white blood cells) 3 weeks later.

What is the difference between Hodgkin and Non-Hodgkin lymphoma?

Hodgkin has Reed-Sternberg cells (large, multinucleated B cells). Non-Hodgkin is more common and includes Burkitt's lymphoma.

What is the HSC niche?

The bone marrow microenvironment that supports haematopoietic stem cells. It provides signals to keep HSCs alive, dormant, or trigger differentiation.

What are the two main HSC niches in bone marrow?

1) Peri-arteriolar niche (keeps HSCs dormant). 2) Peri-sinusoidal niche (more active HSCs, undergoing differentiation).

What is CXCL12 and what does it do?

A chemokine secreted by niche cells. It binds to CXCR4 on HSCs to retain them in the bone marrow.

What is SCF and what does it do?

Stem cell factor (SCF) is secreted by niche cells. It is essential for HSC maintenance.

What happens when the HSC niche is disrupted?

HSCs can multiply uncontrollably, leading to leukaemia.

Complete the sentence: "Leukemia is classified by how quickly it progresses (acute vs ______) and which blood cells are affected (______ vs myeloid).",chronic / lymphoid

What is the most common type of cancer in children?

Leukaemia (accounts for about 1/3 of childhood cancers).

What are the risk factors for leukaemia?

High levels of radiation, benzene exposure, chemotherapy, Down syndrome, strong family history.

What is the difference between lymphoid and myeloid leukaemia?

Lymphoid = affects cells that become lymphocytes. Myeloid = affects cells that become red blood cells, platelets, and other white blood cells.

Complete the sentence: "BCR-ABL is a constitutively active ___________ kinase that drives uncontrolled proliferation in CML.",tyrosine