haematological malignancies Flashcards
what is leukaemia?
it is tumours of the blood or haematopoietic lineages
what are the classifications of leukaemia?
they can be acute or chronic or myeloid (platelets, monocytes, granulocytes and erythrocytes) or lymphoid (B cells, T cells or NK cells)
what is lymphoma?
it is tumours of the lymphocytes or the immune/lymphatic system
what are some types of lymphoma?
Burkitt, diffuse large B cell, marginal zone and follicular
what are the patient determinant outcomes and their classifications?
tumour, treatment and host
in host - age and performance status
in treatment - drug sensitivity and resistance
in tumour - paraneoplastic activity, tumour burden, invasive potential, growth rate and tumour type
what is used in diagnosis?
stain, microscopy, morphology, cytology, EM, PCR, sequencing, alternative proteomics and probe based RNA analysis
what determines the tumour classifications?
immune response, metastatic potential and metabolic activity and oncogenic events
what determines the host characteristics?
the drug metabolism and toxicity
what determines the treatment?
the DNA damage response, apoptotic response, resistance pathways and therapeutic target expression
what are identified in diagnosis?
disease defining point mutations and translocations, myeloproliferative disorders and lymphomas and leukaemias
what aids the prognostication and treatment selection?
the DNA translocations and deletions defining prognostic groups and treatment choices - leukaemia and lymphoma, the immunoglobulin gene mutation load defining risk
how would you monitor, assess response and predict relapse in disease?
monitor the translocations
what are two outcomes in chromosomal translocations?
there are fusion genes and gene deregulation
in myeloid leukaemia what is the result?
aberrant fusion protein from the fused coding regions of two promoter genes
what is the result in B cell lymphoma?
the expression of one gene is controlled by the promoter of the other gene - deregulation
how can you identify these mutated genes?
PCR and logarithmic expansion of target DNA or FISH
what are the characteristics of PCR to define translocations?
only over a small size range, highly sensitive and specific, gene level, need consistent junction and precise sequence
what are the advantages and disadvantages of using FISH?
it is at the chromosomal level over a large size. There is no need to know the specific sequence and have a consistent and it is specific however it is less sensitive.
what are the two types of translocation?
promoter/enhancer substitution or fusion gene translocation
what is the difference between the two types of translocation?
in fusion gene there is a predictable break point and mRNA is processed to remove introns whereas in promoter there is no predictable break point and no abnormal mRNA
where is fusion and promoter translocations most commonly found?
fusion - most commonly found in myeloidleukaemias
promoter - lymphomas