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Molecular Basis of Disease > Haematopoiesis and haematological malignancies > Flashcards

Haematopoiesis and haematological malignancies Flashcards

1
Q

What is haematopoiesis?

A

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

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2
Q

Which cells are found in the bone marrow?

A

Nucleated embryonic red blood cells

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3
Q

Which process happens in the bone marrow?

A

Site of white cell production

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4
Q

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

A

Venesection

Lymph node aspirates and excision

Bone marrow aspirate and trephine bodies

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5
Q

What is venesection used for?

A

Assess mature blood cells

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6
Q

What are lymph node aspirates used for?

A

Assess lymphopoiesis

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7
Q

What are bone marrow aspirate and trephine biopsies used for?

A

Stem cells

Hematopoiesis

Early lymphopoiesis

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8
Q

What is the difference between bone marrow and trephine biopsies?

A

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

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9
Q

Which haematopoietic lineages do haematopoietic stem cells give rise to?

A

Lymphoid

Myeloid

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10
Q

How are stem cells differentiated to the target cellls?

A

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

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11
Q

How often to stem cells divide in humans?

A

Once a year

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12
Q

How many times do stem cells divide before they apoptose?

A

70 times before apoptosis

20 of these divisions occur before the birth of a man

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13
Q

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

A

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

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14
Q

How can stem cells be identified?

A

In vivo assays

Expression of CD34+

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15
Q

How can progenitor cells be identified?

A

In vitro assays

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16
Q

Which assays are used to identify progenitor cells?

A

Colony forming assays

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

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17
Q

How can precursor cells be identified?

A

Morphologically recognisable

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18
Q

How can end cells be identified?

A

Fully differentiated

Have short lifespans

Negative for CD34 marker

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19
Q

Describe the structure of neutrophils

A

Lobed nuclei

Large structure

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20
Q

Describe the structure of lymphocytes

A

Large, granulated nuclei

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21
Q

How do stem cells divide?

A

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

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

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22
Q

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

A

ECM components

Growth factors

Mechanical forces

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23
Q

How do growth factors increase cell populations?

A

Inducing cells into the cell cycle

Shortening the cell cycle time

Instructing the lineages

Increasing mature cell survival

Inhibiting progenitor cell apoptosis

24
Q

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

TRUE or FALSE

A

FALSE

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

25
Q

Examples of early growth factors

A

IL-1

IL-6

EPO

26
Q

Examples of intermediate growth factors

A

IL-3

IL-5

EPO

GM-CSF

27
Q

Examples of late growth factors

A

G-CSF

M-CSF

28
Q

What is an important function of growth factors?

A

Enable a rapid response to stress

Allow us to differentiate stem cells to the cell types we need

29
Q

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

A

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

30
Q

Explain the TPO production feedback loop

A

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

31
Q

What are the 3 main types of haematological malignancies?

A

Leukemia

Lymphoma

Multiple myeloma

32
Q

What happens in lymphoma?

A

Excess lymphocytes in lymph node and bone marrow

33
Q

What happens in multiple myeloma?

A

Excess plasma cells in blood and bone marrow

34
Q

What happens in leukemia?

A

Excess white cells in the blood and bone marrow

35
Q

What are the two types of leukemia?

A

Acute

Chronic

36
Q

What can acute and chronic leukemia be further differentiated into?

A

Myeloid

Lymphoid

37
Q

Characteristics of acute leukemia

A

Disease progresses quickly

Often presents with bone marrow failure

Malignant cells have undifferentiated phenotype

38
Q

Characteristics of malignant cells in acute leukemia

A

Malignant cells have undifferentiated phenotypes

39
Q

How do patients with chronic leukemia present?

A

Present with features caused by cellular burden - organomegaly and gout

Bone marrow failure is late feature

Behaves more indolently so normally diagnosed incidentally

40
Q

Characteristics of malignant cells in chronic leukemia

A

Malignant cells are mature

41
Q

What differentiates chronic and acute leukemia?

A

Progression of the condition

Bone marrow failure presentation

Phenotype of the cells

42
Q

Which 3 techniques are used to classify and diagnose leukemia?

A

Microscopy

Cytogenetics

Molecular genetics

43
Q

Which samples are used to diagnose leukemia?

A

Blood

Bone marrow aspirate

Trephine

44
Q

Examples of cytogenetic techniques used to diagnose a patient with leukemia

A

G-banding

FISH

45
Q

Why is cytogenetics important?

A

Reveals genetic mutations that can affect the prognosis for the good or bad

Monosomy 7 = poor diagnosis
APML = good prognosis

46
Q

Examples of molecular genetic techniques to diagnose patient with leukemia

A

PCR

Sequencing

47
Q

Clinical features of acute leukemia

A

Bone marrow failure

Organ infiltration

Metabolic

Coagulopathy

Pancytopenia

48
Q

How does bone marrow failure present?

A

Anaemia

Bleeding

Infection

49
Q

Complications of pancytopenia

A

Infections

Blood loss

Brain fungal infection

50
Q

Examples of organ infiltration observed in acute leukemia

A

Hepatosplenomegaly

CNS

Gums

Skin

51
Q

Examples of pancytopenia

A

Thrombocytopenia

Leucopenia

52
Q

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

A

Supportive

Specific

Support for psychological and social impacts of disease/treatment

53
Q

Examples of supportive treatments

A

Keep RBC, platelet and infection under control

54
Q

Examples of specific treatments

A

Remission induction via cytotoxic chemotherapy

Consolidation chemotherapy

Maintenance chemotherapy

Allogenic SCT

55
Q

Is outcome of acute leukemia treatment age-dependant?

A

Yes

Outcomes in childhood ALL are better than adult ALL

Molecular Basis of Disease (28 decks)

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