Leuk Flashcards
Define leukaemia
→malignant disorders of haematopoietic stem cells characteristically associated with increase number of white cells in bone marrow or/and peripheral blood.
What are the two features of haematopoietic stem cells?
→Multipotent- can give rise to cells of every blood lineage
→Self maintaining- a stem cell can divide to produce more stem cells
What are the three features of progenitor cells?
→Can divide to produce many mature cells
→But cannot divide indefinitely
→Eventually differentiate and mature
What is the difference in morphology of undifferentiated and differentiated progenitor cells?
→cannot tell the difference between them morphologically because they do not show the characteristics of mature cells.
What is meant by leukaemia being clonal?
→all the malignant cells derive from a single mutant stem cell.
What are the first symptoms of all leukaemia?
→Abnormal bruising-commonest
→Repeating abnormal infection
→Sometimes anaemia
→Fever
What are the three ways of diagnosing leukaemia?
→Peripheral blood blasts test (PB)
→ Bone marrow test/biopsy (BM)
→Lumbar puncture
Why is peripheral blood test used in leukaemia diagnosis?
→looks for blasts and cytopenia.
→ if >30% blasts are suspected of acute leukaemia.
Where is bone marrow taken from?
→taken from pelvic bone and results compared with PB.
Why is lumbar puncture used in leukaemia diagnosis?
→to determine if the leukaemia has spread to the cerebral spinal fluid (CSF)
What techniques are involved in molecular and pathophysiological characterisation of leukaemia testing?
→Cytomorphology →Immunophenotyping →Next Generation Sequencing (NGS) →Flow cytometry →Fluorescence in situ Hybridation (FISH)
What type of leukaemia are sometimes hereditary?
→Chronic Lymphocytic Leukaemia (CLL)
What are some chromosome aberrations which may be genetic risk factors for leukaemia?
→Translocations (e.g. BCR-ABL in CML).
→Numerical disorders (e.g. trisomy 21-Down syndrome).
What are some inherited immune system problems that predisposes to leukaemia?
→Ataxia-telangiectasia,
→Wiskott-Aldrich syndrome
What are some genetic mutations that predisposes to leukaemia?
→TP53- Li-Fraumeni syndrome,
→NF1-Neurofibromatosis
What are some environmental risk factors that predisposes to leukaemia?
→Radiation exposure
→Exposure to chemicals and chemotherapy
→Immune system suppression
What are some risk factors linked to childhood leukaemia?
→Exposure to electromagnetic fields →Foetal exposure to hormones →Parent’s smoking history →Infections early in life →Mother’s age when child is born
What are the classifications of leukaemia?
→Acute Lymphoid Leukaemia (ALL) →Acute Myeloid Leukaemia (AML) →Chronic Lymphoid Leukaemia (CLL) →Chronic Myeloid Leukaemia (CML)
What is acute leukaemia?
→rapid onset and short but severe course
What are characteristics of acute leukaemia?
→Undifferentiated leukaemia
→uncontrolled clonal and accumulation of immature white blood cells (-blast)
→High number of blasts in blood
Which cells in the bone marrow are involved in acute leukaemia?
→myeloblast
→lymphoblast
What are the characteristics of chronic leukaemia?
→Differentiated leukaemia
→uncontrolled clonal and accumulation of mature white blood cells (-cyte)
Which cells in the bone marrow are involved in chronic leukaemia?
→-cytes
What is the age of onset for acute and chronic Leukaemia?
→ acute= children
→chronic= insidious
What is the onset like for acute and chronic leukaemia?
→ acute= sudden, weeks to months
→chronic= insidious, years
What is the WBC count like in acute and chronic leukaemia?
→acute = Variable- high rates of blasts →chronic= high
What are the two types of acute leukaemia?
→Acute Lymphoblastic Leukaemia (ALL)- 75%
→Acute Myeloblastic Leukaemia (AML)-20%
What are the typical symptoms of acute leukaemia due to bone marrow suppression?
→Thrombocytopenia: nosebleed →Neutropenia →anaemia →night sweats →frequent infections
Which is the most common childhood cancer?
→Acute Lymphoblastic Leukaemia
What is the cells classification of ALL?
→B-cell & T-cell leukaemia
What is the treatment for ALL?
→Chemotherapy
What is the outcome like for ALL treatment?
→5 year event-free survival (EFS) of 87%
→1 out of 10 ALL patients relapse.
→Remission in 50% percent of them after second chemotherapy treatment or bone marrow transplant.
Why are adult ALL prognosis poor?
→because disease presents different cell of origin and different oncogene mutations.
What is the prevalence of AML?
→rare in children
How is AML classified?
→based on FAB system (French-American-British): M0-M7
What are the treatments for AML?
→Chemotherapy,
→monoclonal antibodies (immunotherapy) +/- allogeneic bone marrow transplant.
What is the outcome like for AML?
→5 year event-free survival (EFS) of 50-60%.
How is AML and ALL differentiated in diagnosis?
→use cytomorphological studies
What are the symptoms of CLL?
→Recurrent infections due to : →neutropenia, → anaemia, →thrombocytopenia, →lymph node enlargement, →hepatosplenomegaly.
What is the treatment for CLL?
→Regular chemotherapy to reduce cell numbers
What is the outcome like for CLL?
→5-year event-free survival (EFS) of 83%
→ Many patients survive >12 years.
What is the peak age for CML?
→peak rate = 85-89y/o
What are the symptoms of CML?
→Often asymptomatic
→discovered through routine blood tests.
How is CML diagnosed?
→Very high white cells count (neutrophilia) in blood and bone marrow,
→presence of Philadelphia chromosome
What is the treatment for CML?
→Targeted therapy: Imatinib
→allogeneic bone marrow transplant
Why is the BCR-ABL protein an oncogene?
→has constitutive (unregulated) protein tyrosine kinase activity
→ABL has a strong promotor and ABL gene encodes a protein tyrosine kinase
What does unregulated BCR-ABL tyrosine kinase activity cause?
→Proliferation of progenitor cells in the absence of growth factors
→Decreased apoptosis
→Decreased adhesion to bone marrow stroma
What might a detection of minimal residual disease mean for treatment?
→clue as to the efficacy of treatment
How does Imatinib work?
→Drugs that specifically inhibit BCR-ABL
→imatinib competes with ATP which binds to BCR-ABL fusion
→ used to detect minimal residual disease
What are the differences between targeted therapies and chemotherapy?
→Targeted Act on specific molecular targets associated with cancer whereas chemotherapy Act on all rapidly dividing cells (cancerous and normal)
→targeted is cytostatic whereas chemotherapy is cytotoxic
→targeted used oral agents whereas chemotherapy is mainly intravenous with some oral agents
