14: Leukaemia Flashcards
What is the site disease in Leukaemia?
Leukaemia is “cancer of the blood”, more specifically
- bone marrow disease (not all patients have abnormal cells in the blood)
- it is cancer in lymphoid/myeloid stem cells
What are the different types of cells that can be affected in leukaemia?
-
Pluripotent haematopoietic Stem Cell
- would lead to mixed phenotype leukaemia
-
Myeloid Stem Cell
- Myeloid leukaemia
-
Lymphoid Stem Cell
- Lmphatic leukaemias
- Pre B Lymphocyte
- Pro T Lymphocyte
Explain and summarise the development of leukaemias
Leukaemias need
-
multiple mutations in a single myelod/lympoid stem cell
- leading to a potency of cell for increased proliferation, differentiation, or cell survival
- Leading to expansion of the leukaemic clone
Why can’t the concepts of invasion and metastisis not be applied to leukaemias?
Because blood cells (also haematopoietic stem cells) are physiologically found in the body and infiltrate tissues
How are “benign” and “malignant” forms of leukaemia determined and named?
The words chronic and acute are used
- Chronic
- behave in a “benign” manner, the disease goes on for a long time
- Acute
- behaves “malignant”, untreated the disease is agressive and the patient dies rapidly
How are the chronic and acute forms of leukaemias derived from lymphoid precursor cells called?
–Acute lymphoblastic leukaemia (ALL)
–Chronic lymphocytic leukaemia (CLL)
How are leukaemias derived from Myeloid cells called?
Acute/Chronic myeloid leukaemias
What are the important factors in the development of leukaemia?
Requires a series of mutations (basically just like any other cancer)
Importnatn identified mutations include
- There are normally multiple genes affected, in particular transcription factors so that the transcription of multiple genes is affected and cell behavior profoundly disturbed
- in proto-oncogenes
- creatin of a novel gene (chiameric/fusion gene)
- mutation in promoter/enhancer of a structurally normal gene
- loss of TSG
What are certain risk factors to the development of leukaemias?
Some inherited mutations e.g. in
- down syndrome
- defects in DNA repair etc.
Or exposure to
- Irradiation
- Anti-cancer drugs
- Cigarette smoking
- Chemicals—benzene
What happens during AML?
, cells continue to proliferate but they no longer mature so there is
- Built up of immautre (myeloblast) cells in the BM and spread into the blood
- Together with a Failure to produce normal cells e.g. neutrophils, monocytes, erythrocytes, platelets
Failure of production of End Cells
What are the genetic causes for the production of AML?
- Often Transcription factors involved
- Transcripition of multiple genes affected
- Normal function of proteins are not possible (because they are supressed by an oncogene product)
–> Cell behaviour is profoundly disturbed
What are the genetic causes for developement of CML?
mutations usually affect a gene encoding a protein in the signalling pathway between a cell surface receptor and the nucleus
What happes during CML?
- cell kinetics and funcitons are not as seriously affected as in AML
- BUT: reduced apoptosis and increase proliferation –> slow progression of leukaemic clones
Increased production of end cells
What is the Differnce between acute and chronic LL?
- •Acute lymphoblastic leukaemia (ALL)
- increase in immature cells (lymphoblasts)
- no maturation into B and T cells
- Chronic lymphoid leukaemias (CML)
- , the leukaemic cells are mature,
- although abnormal, T cells or B cells
What are the general symptoms of leukaemia?
What is the underlying cause?
Normally caused by an accumulation of cells or infiltration of tissues
- bone pain (if acute)
- high metabolic rate and high proliferation
- hepatomegaly and splenomegaly
- extramedullary blood formation (due to no more formation in BM) and increased infiltration of tissues by cells
- lymphadenopathy (if lymphoid),
- thymic enlargement (if T lymphoid),
- skin infiltration
- overall: increased metabolic rate
- weight loss sweating, low grade fever
What are symptoms of ALL?
Resulting from accumulation of abnormal cells (+inflitration of tissues) leading to:
- Bone pain
- Hepatomegaly
- Splenomegaly
- Lymphadenopathy
- Thymic enlargement
- Testicular enlargement
And Resulting from crowding out of normal cells (ANT symptoms)
- Anaemia casuing Fatigue, lethargy, pallor, breathlessness
- Neutropenia: Fever and other features of infection
- Thrombocytopenia: Bruising, petechiae, bleeding
What are haematological findings in ALL?
- Leucocytosis with lymphoblasts in the blood
- Anaemia (normocytic, normochromic)
- Neutropenia
- Thrombocytopenia
- Replacement of normal bone marrow cells by lymphoblasts
Explain the importance of immunophenotyping in ALL
It is important to determine the cause of the Leukaemia
- B cell? T cell?
- Done by flourescent analysis of cells (binding to CD factors of cells)
