Haematopoiesis and haematological malignancies

Question 1

What is haematopoiesis?

Answer 1

Process which regulates the proliferation of stem cells and their differentiation into mature blood cells

Question 2

Which cells are found in the bone marrow?

Answer 2

Nucleated embryonic red blood cells

Question 3

Which process happens in the bone marrow?

Answer 3

Site of white cell production

Question 4

Which ways are there to study the health of the bone marrow?

Answer 4

Venesection

Lymph node aspirates and excision

Bone marrow aspirate and trephine bodies

Question 5

What is venesection used for?

Answer 5

Assess mature blood cells

Question 6

What are lymph node aspirates used for?

Answer 6

Assess lymphopoiesis

Question 7

What are bone marrow aspirate and trephine biopsies used for?

Answer 7

Stem cells

Hematopoiesis

Early lymphopoiesis

Question 8

What is the difference between bone marrow and trephine biopsies?

Answer 8

Bone marrow uses blood cells stained in suspension

Trephine views the structure of the bone marrow. Carries significant risk so is only carrried out in certain circumstances

Question 9

Which haematopoietic lineages do haematopoietic stem cells give rise to?

Answer 9

Lymphoid

Myeloid

Question 10

How are stem cells differentiated to the target cellls?

Answer 10

Stem cells -> progenitor cells -> precursor cells -> end cells

Question 11

How often to stem cells divide in humans?

Answer 11

Once a year

Question 12

How many times do stem cells divide before they apoptose?

Answer 12

70 times before apoptosis

20 of these divisions occur before the birth of a man

Question 13

What happens to the properties of stem cells as they differentiate?

Answer 13

Properties are lost as the cells differentiate in expense of their specialisation

Question 14

How can stem cells be identified?

Answer 14

In vivo assays

Expression of CD34+

Question 15

How can progenitor cells be identified?

Answer 15

In vitro assays

Question 16

Which assays are used to identify progenitor cells?

Answer 16

Colony forming assays

Placed in semi-solid medium and allowed to differentiate to blood cell types in 2-3 weeks

Question 17

How can precursor cells be identified?

Answer 17

Morphologically recognisable

Question 18

How can end cells be identified?

Answer 18

Fully differentiated

Have short lifespans

Negative for CD34 marker

Question 19

Describe the structure of neutrophils

Answer 19

Lobed nuclei

Large structure

Question 20

Describe the structure of lymphocytes

Answer 20

Large, granulated nuclei

Question 21

How do stem cells divide?

Answer 21

Mostly asymetrically, by making one stem cell and one differentiated cell

Sometimes symetrically, by making either two differentiated cells or two new stem cells

Question 22

Which factors affect the differentiation of progenitors into the differentiated cell types

Answer 22

ECM components

Growth factors

Mechanical forces

Question 23

How do growth factors increase cell populations?

Answer 23

Inducing cells into the cell cycle

Shortening the cell cycle time

Instructing the lineages

Increasing mature cell survival

Inhibiting progenitor cell apoptosis

Question 24

When progenitors differentiate into a cell type, they can go back to their progenitor state

TRUE or FALSE

Answer 24

FALSE

Differentiated cell types can’t go back to their progenitor state

Question 25

Examples of early growth factors

Answer 25

IL-1 IL-6 EPO

Question 26

Examples of intermediate growth factors

Answer 26

IL-3 IL-5 EPO GM-CSF

Question 27

Examples of late growth factors

Answer 27

G-CSF M-CSF

Question 28

What is an important function of growth factors?

Answer 28

Enable a rapid response to stress Allow us to differentiate stem cells to the cell types we need

Question 29

Example of growth factors affecting the differentiation of stem cells in response to stress

Answer 29

Bleeding results in release of the GF EPO which increases red blood cell production by increasing stem cell differentiation

Question 30

Explain the TPO production feedback loop

Answer 30

Stimulated when clotting is needed in response to cut Growth factors respond to stress TPO induces stem cells to differentiate to megakaryocytes Megakaryocytes give rise to platelets expressing sialic acid Sialic acid receptor is lost with age Platelets then bind to hepatic cells -> increases TPO production -> increases platelet formation

Question 31

What are the 3 main types of haematological malignancies?

Answer 31

Leukemia Lymphoma Multiple myeloma

Question 32

What happens in lymphoma?

Answer 32

Excess lymphocytes in lymph node and bone marrow

Question 33

What happens in multiple myeloma?

Answer 33

Excess plasma cells in blood and bone marrow

Question 34

What happens in leukemia?

Answer 34

Excess white cells in the blood and bone marrow

Question 35

What are the two types of leukemia?

Answer 35

Acute Chronic

Question 36

What can acute and chronic leukemia be further differentiated into?

Answer 36

Myeloid Lymphoid

Question 37

Characteristics of acute leukemia

Answer 37

Disease progresses quickly Often presents with bone marrow failure Malignant cells have undifferentiated phenotype

Question 38

Characteristics of malignant cells in acute leukemia

Answer 38

Malignant cells have undifferentiated phenotypes

Question 39

How do patients with chronic leukemia present?

Answer 39

Present with features caused by cellular burden - organomegaly and gout Bone marrow failure is late feature Behaves more indolently so normally diagnosed incidentally

Question 40

Characteristics of malignant cells in chronic leukemia

Answer 40

Malignant cells are mature

Question 41

What differentiates chronic and acute leukemia?

Answer 41

Progression of the condition Bone marrow failure presentation Phenotype of the cells

Question 42

Which 3 techniques are used to classify and diagnose leukemia?

Answer 42

Microscopy Cytogenetics Molecular genetics

Question 43

Which samples are used to diagnose leukemia?

Answer 43

Blood Bone marrow aspirate Trephine

Question 44

Examples of cytogenetic techniques used to diagnose a patient with leukemia

Answer 44

G-banding FISH

Question 45

Why is cytogenetics important?

Answer 45

Reveals genetic mutations that can affect the prognosis for the good or bad Monosomy 7 = poor diagnosis APML = good prognosis

Question 46

Examples of molecular genetic techniques to diagnose patient with leukemia

Answer 46

PCR Sequencing

Question 47

Clinical features of acute leukemia

Answer 47

Bone marrow failure Organ infiltration Metabolic Coagulopathy Pancytopenia

Question 48

How does bone marrow failure present?

Answer 48

Anaemia Bleeding Infection

Question 49

Complications of pancytopenia

Answer 49

Infections Blood loss Brain fungal infection

Question 50

Examples of organ infiltration observed in acute leukemia

Answer 50

Hepatosplenomegaly CNS Gums Skin

Question 51

Examples of pancytopenia

Answer 51

Thrombocytopenia Leucopenia

Question 52

What are the three main types of treatment of acute leukemia?

Answer 52

Supportive Specific Support for psychological and social impacts of disease/treatment

Question 53

Examples of supportive treatments

Answer 53

Keep RBC, platelet and infection under control

Question 54

Examples of specific treatments

Answer 54

Remission induction via cytotoxic chemotherapy Consolidation chemotherapy Maintenance chemotherapy Allogenic SCT

Question 55

Is outcome of acute leukemia treatment age-dependant?

Answer 55

Yes Outcomes in childhood ALL are better than adult ALL