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Biology of Cancer > Week 8 - Chronic Myeloid Leukaemia > Flashcards

Week 8 - Chronic Myeloid Leukaemia Flashcards

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1
Q

What is the definition of Leukaemia?

A

Leukaemia’s are a group of diseases that are characterised by malignant overproduction of WBC’s or their immature pre-cursors.

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2
Q

What is the difference between lymphoid and myeloid leukaemia’s?

A

Lymphoid affects cells of lymphocyte lineage - B-Cells more common, T-Cells rare

Myeloid affects cells of the non-lymphocytic lineage, blood cell lineage - neutrophils and their pre-cursors, as well as erythroid, platelet and basophil lineages.

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3
Q

What does Acute mean with regards to cancer and how does that differ from chronic?

A

Acute - disease with rapid onset and short but severe course

Chronic - Long term disease

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4
Q

What are acute leukaemia’s defined as?

A

Uncharacterised Leukaemia’s - Charactersied by immature white cells (Blast Cells).

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5
Q

What are chronic leukaemia’s defined as?

A

Differentiated Leukaemia’s - characterised by mature white blood cells.

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6
Q

What is the nomenclature given to acute and chronic lymphoid leukaemia’s?

A

Acute LYMPHOBLASTIC Leukaemia

Chronic LYMPHOCYTIC Leukaemia

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7
Q

What is the nomenclature given to acute and chronic myeloid leukaemia’s?

A

Acute MYELOBLASTIC Leukaemia

Chronic GRANULOCYTIC Leukaemia

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8
Q

Name the 4 types of cells that represent the progression of Haematopoiesis.

A

Stem cells

Progenitor cells

Immature pre-cursors

Mature cells

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9
Q

Name two characteristics of Haematopoietic Stem Cells and describe them.

A

Pluripotent - give rise to all cells of blood lineage

Self-maintaining - can divide to produce more stem cells

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10
Q

Name two characteristics of Progenitor cells and describe them.

A

Undifferentiated - Morphologically indifferent to stem cells

Committed - Committed to specific cell lineage

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11
Q

Name the 6 forms of the process from a Myeloblast to a Segmented Neutrophil (inclusive).

A

Myeloblast

Promyelocyte

Myelocyte

Metamyelocyte

Band

Segmented Neutrophil

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12
Q

Name 3 presentations of CML.

A

Anaemia - Fatigue & breathlessness

Splenomegaly - LU Quadrant fullness or pain

Weight Loss

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13
Q

Name 2 diagnostic features of CML.

A
  1. Neutrophilia with left shift

2. Presence of Philidelphia Chromosome/BCR-ABL gene re-arrangement

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14
Q

What are the 2 phases seen in CML and how long do they last?

A

Chronic phase - may last from months to years (untreated)

Accelerated Phase/Blast Crisis - Resembles acute leukaemia - days/weeks.

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15
Q

Name 3 treatments of CML.

A
  1. Chemotherapy with cytotoxic drugs
  2. Interferon-alpha
  3. SCBMT
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16
Q

Describe what effects chemotherapy causes. (2)

A
  1. Kill leukaemic cells and normally dividing cells such as GI epithelium, hair follicles etc.
  2. It controls the symptoms but does not eliminate the disease.
17
Q

Describe the effects of Interferon-Alpha

A
  1. Suppresses leukaemic haematopoiesis
  2. More effective than cytotoxic drugs
  3. Not curative
  4. Unpleasant side effects - flu, fatigue, low blood count.
18
Q

Describe the process of giving SCBMT and its effects.

A
  1. Give intense chemotherapy and total body irradiation
  2. Wipes out leukaemic cells and normal stem cells
  3. Reconstitute bone marrow by transplanted stem cells

Can be a cure

19
Q

Describe the issues with SCBMT.

A
  1. Shortage of HLA (MHC) matched donors

2. High mortality of the procedure for older and/or sicker patients.

20
Q

What is the link between CML and Philidelphia chromosome.

A

95% of CML cases have detectable PC

21
Q

Name the two regions where breakpoint usually occur in the ABL gene.

A

In the introns following Exon numbers 1a and 1b.

22
Q

Name the area where breakpoints occur in the BCR gene.

A
  1. Introns within the Major Breakpoint Cluster Region - M-Bcr - before exon 11 and before exon 16.
  2. Minor breakpoint cluster region - m-bcr region - after exon 1 and before exon 2
  3. Micro breakpoint cluster region - μ-bcr region - after exon 1 - and before exon 16
23
Q

Other than CML which other condition is Philidelphia chromosome seen in?

A

Adult ALL

24
Q

How are BCR-ABL positive cells detected?

A

Through reverse transcription PCR

25
Q

What type of PCR is used to monitor therapy?

A

Quantitative RT-PCR

26
Q

What is the ABL protein?

A

A protein tyrosine kinase

27
Q

What is the process of transfecting the BCR-ABL gene into a mouse?

A
  1. Package BCR-ABL gene (with LTR regions) as a retrovirus
  2. Infect with Bone Marrow Cells
  3. Transplant into recepient mouse.
28
Q

How is BCR-ABL’s ability to cause CML detected?

A

Specific inactivation of BCR-ABL using siRNA

CML cells enter apoptosis

Biology of Cancer (18 decks)

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