leukemia DD Flashcards
what are the associated symptoms of leukemia?
- pallor;
- lethargy;
- pharyngitis;
- recurrent infections;
- easy bruising;
- pyrexia;
- night sweats;
- bone pain;
- flu-like symptoms;
- lymphadenopathy;
- splenomegaly;
- hepatomegaly.
what are the 4 major classifications of leukaemia?
- Acute Lymphoblastic Leukaemia (ALL)
- Acute Myeloid Leukaemia (AML)
- Chronic Lymphocytic Leukaemia (CLL)
- Chronic Myeloid Leukaemia (CML)
what is the difference between acute vs chronic leukaemia?
- Acute leukaemia is fast-growing and can progress quickly without treatment
- Acute leukaemia cells multiply before any immune function has developed
- Chronic leukaemia is slow-growing
- Chronic leukaemia cells have immature, limited immune function
how do you classify leukaemia?
- Morphology-Cornerstone, but some share
similar morphology - Immunophenotype-Quantitative determination of cell lineage (e.g. B-, T- or NK-cell)
- Genotype-Specific translocations in
lymphomas
what is the difference between leukaemia and lymphoma?
leukemia is cancer of the blood cells that usually starts in the bone marrow and often travels through the bloodstream
lymphoma is cancer of the lymphatic system that usually originates in lymph nodes or, sometimes, the spleen.
how does immunophenotyping of leukaemia work?
- Malignant cells may show altered morphology
- Immunophenotyping (e.g. by flow cytometry) can identify cell lineage
- CD proteins on cell surface used as markers
- B-Cells have a marker called CD19
what are the risk factors for acute lymphocytic leukaemia?
- Radiation, pesticides, viruses (EBV, HIV) – thought to contribute
- Inherited syndromes
race/ethnicity
what is acute lymphoblastic leukaemia?
Acute lymphoblastic leukaemias are neoplasms of precursor B- and T-cells, called lymphoblasts
* Accumulation of lymphoblasts in bone marrow and peripheral blood
what is the most common type of acute lymphoblastic leukaemia?
Can be malignancy of B-cell (85%) or T-cell (15%) lineage
where does acute lymphoblastic leukaemia originate and spread to?
ALL starts in Bone Marrow, while lymphomas start in lymph nodes and spreads to Bone Marrow
– At diagnosis, malignant cells can be found at both locations – hard to
diagnose leukaemia Vs lymphoma
what investigations are done for ALL?
- Full blood count
– Normochromic normocytic anaemia (normal-sized RBC, normal Hb
content)
– Neutropenia (low neutrophil count)
– Thrombocytopenia (low platelet count)
– WBC count can be increased (>200 x 109), normal, or decreased - Blood film
– Variable number of blast cells - Bone marrow
– Hypercellular, with >20% blasts
how are ALL blast cells characterised?
- Morphology
- Immunological tests
- Cytogenetic analysis
- Blasts are larger than lymphocytes
- Morphology similar to
myeloblasts - Requires immunophenotyping or cytochemical stains
what investigations do you do for ALL?
- Immunophenotype
– Markers of B-cells (CD19) or T-cells (CD7) lineage - Immunoglobulin (B-cell) and TCR (T-cell) genes
– Recombination occurs early in immunoglobulin and T-cell receptor
production, in primary lymphoid tissues (bone marrow / thymus)
– Clonal populations carry the same VDJ rearrangements
– Polyclonal indicates reactive lymphocytes, e.g. due to infection - Molecular genetics
– Detection of cytogenetic abnormalities and mutations, etc.
what is the pathogenesis of ALL?
*Normally the first mutation occurs in the foetus, in early lymphoid
progenitor cells
– Cells continue to undergo alterations in the bone marrow, forming
lymphoblasts (pro-B cells) and prolymphocytes (pre-B cells)
– Germline mutation in <5% of cases
what causes the second genetic event in childhood?
– Potentially associated with childhood infection and exposures (e.g. ionising radiation)
– May be indirectly promoted through abnormal response to a common
infection (i.e. not due to a specific virus), esp. in under-exposed infants
what are the genes involved in ALL?
Genes identified for this disease are directly involved in blood cell proliferation and differentiation
what are the genetic observed in ALL patients?
– Gene variability
– Chromosomal alterations
– Observation of ‘chimeric’ proteins
– Chimera is a hybrid creature from
Greek Mythology
