Week 8 - Chronic Myeloid Leukaemia Flashcards
What is the definition of Leukaemia?
Leukaemia’s are a group of diseases that are characterised by malignant overproduction of WBC’s or their immature pre-cursors.
What is the difference between lymphoid and myeloid leukaemia’s?
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.
What does Acute mean with regards to cancer and how does that differ from chronic?
Acute - disease with rapid onset and short but severe course
Chronic - Long term disease
What are acute leukaemia’s defined as?
Uncharacterised Leukaemia’s - Charactersied by immature white cells (Blast Cells).
What are chronic leukaemia’s defined as?
Differentiated Leukaemia’s - characterised by mature white blood cells.
What is the nomenclature given to acute and chronic lymphoid leukaemia’s?
Acute LYMPHOBLASTIC Leukaemia
Chronic LYMPHOCYTIC Leukaemia
What is the nomenclature given to acute and chronic myeloid leukaemia’s?
Acute MYELOBLASTIC Leukaemia
Chronic GRANULOCYTIC Leukaemia
Name the 4 types of cells that represent the progression of Haematopoiesis.
Stem cells
Progenitor cells
Immature pre-cursors
Mature cells
Name two characteristics of Haematopoietic Stem Cells and describe them.
Pluripotent - give rise to all cells of blood lineage
Self-maintaining - can divide to produce more stem cells
Name two characteristics of Progenitor cells and describe them.
Undifferentiated - Morphologically indifferent to stem cells
Committed - Committed to specific cell lineage
Name the 6 forms of the process from a Myeloblast to a Segmented Neutrophil (inclusive).
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Band
Segmented Neutrophil
Name 3 presentations of CML.
Anaemia - Fatigue & breathlessness
Splenomegaly - LU Quadrant fullness or pain
Weight Loss
Name 2 diagnostic features of CML.
- Neutrophilia with left shift
2. Presence of Philidelphia Chromosome/BCR-ABL gene re-arrangement
What are the 2 phases seen in CML and how long do they last?
Chronic phase - may last from months to years (untreated)
Accelerated Phase/Blast Crisis - Resembles acute leukaemia - days/weeks.
Name 3 treatments of CML.
- Chemotherapy with cytotoxic drugs
- Interferon-alpha
- SCBMT
Describe what effects chemotherapy causes. (2)
- Kill leukaemic cells and normally dividing cells such as GI epithelium, hair follicles etc.
- It controls the symptoms but does not eliminate the disease.
Describe the effects of Interferon-Alpha
- Suppresses leukaemic haematopoiesis
- More effective than cytotoxic drugs
- Not curative
- Unpleasant side effects - flu, fatigue, low blood count.
Describe the process of giving SCBMT and its effects.
- Give intense chemotherapy and total body irradiation
- Wipes out leukaemic cells and normal stem cells
- Reconstitute bone marrow by transplanted stem cells
Can be a cure
Describe the issues with SCBMT.
- Shortage of HLA (MHC) matched donors
2. High mortality of the procedure for older and/or sicker patients.
What is the link between CML and Philidelphia chromosome.
95% of CML cases have detectable PC
Name the two regions where breakpoint usually occur in the ABL gene.
In the introns following Exon numbers 1a and 1b.
Name the area where breakpoints occur in the BCR gene.
- Introns within the Major Breakpoint Cluster Region - M-Bcr - before exon 11 and before exon 16.
- Minor breakpoint cluster region - m-bcr region - after exon 1 and before exon 2
- Micro breakpoint cluster region - μ-bcr region - after exon 1 - and before exon 16
Other than CML which other condition is Philidelphia chromosome seen in?
Adult ALL
How are BCR-ABL positive cells detected?
Through reverse transcription PCR
What type of PCR is used to monitor therapy?
Quantitative RT-PCR
What is the ABL protein?
A protein tyrosine kinase
What is the process of transfecting the BCR-ABL gene into a mouse?
- Package BCR-ABL gene (with LTR regions) as a retrovirus
- Infect with Bone Marrow Cells
- Transplant into recepient mouse.
How is BCR-ABL’s ability to cause CML detected?
Specific inactivation of BCR-ABL using siRNA
CML cells enter apoptosis
