clinical oncology Flashcards
leukaemia: define leukaemia, explain the difference between lymphoid and myeloid leukaemia, and acute and chronic leukaemia; summarise the clinical, haematological features and genetic features of acute lymphoblastic leukaemia (54 cards)
define leukaemia
bone marrow disease normally causing increased WBC (“white blood”) - hence “cancer of blood”
epidemiology of leukaemia: common and mortality
most common cancers in men/women ages 15-24, main cause of cancer death between 1-34
leukaemia mechanism
mutations in single lymphoid or myeloid stem cell, leading progeny to show abnormalities in proliferation (too rapid), differentiation (don’t reach end cell) or cell survival (too long), leading to steady expansion of leukaemic clone
cells that can be mutated to be involved in leukaemia
pluripotent haematopoietic stem cell (mixed phenotype leukaemia), myeloid stem cell, lymphoid stem cell, pre-B lymphocyte, pre-T lymphocyte
2 hit hypothesis in leukaemia
first mutation gives growth/survival advantage to that line of cells, so expand at expense of normal cells; acquire second mutation to get leukaemia
how is leukaemia different to other cancers: tumours
most cancers exist as solid tumour, with other tumours present in leukaemia patients being uncommon (more often have leukaemic cells replacing normal bone marrow cells and circulating freely in blood stream)
how is leukaemia different to other cancers: cells
haemopoietic and lymphoid cells behave differently from other body cells: normal haemopoietic stem cells can circulate in blood and both stem cells and cells derived from them can enter tissues, and normal lymphoid stem cells recirculate between tissues and blood
how is leukaemia different to other cancers: benign and malignant, and impact on treatment
invasion and metastasis cannot be applied to cells that normally travel around body and enter tissues (must have another way to distinguish benign vs malignant), so treatment must be systemic
what are leukaemias that behave relatively benignly called
chronic
what are leukaemias that behave malignantly called, and outcome if not treated
acute (if not treated, disease is very aggressive and patient dies quite rapidly)
2 classifications of leukaemia
acute vs chronic, lymphoid (B/T cell) vs myeloid (granulocyte, monocyte, erythroid, megakaryocyte)
4 types of leukaemia
acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML)
describe the 2 types of influences which cause a series of mutations in a single stem cell to cause leukaemia (causing characteristics due to proliferation of leukaemic cells and loss of function of normal cells)
some are identifiable oncogenic, while others are random errors that occur throughout life and accumulate in individual cells
3 important leukaemogenic mutations
mutation in known proto-oncogenes, creation of novel gene (e.g. chimaeric or fusion gene when chromosomes translocate), dysregulation of gene when translocation brings it under influence of promoter or enhancer of another gene
what other gene can be affected to contribute to leukaemogenesis
loss of function of tumour-suppressor gene (resulting from deletion or mutation of gene)
what 2 genetic tendencies can increase risk of leukaemia
tendency to increased chromosomal breaks, if cell cannot repair DNA (error persists)
what 4 inherited/other constitutional abnormalities can contribute to leukaemogenesis
Down’s syndrome, chromosomal fragility syndromes, defects in DNA repair, inherited defects of tumour-suppressor genes
4 identifiable causes (not mechanisms) of leukaemogenic mutations
irradiation, anti-cancer drugs, cigarette smoking, chemicals e.g. benzene
why might leukaemia be, in part, an inevitable result of ability of humanity to change through evolution
some mutations appear to be random events rather than caused by exogenous influence, so may result from nature of human genome
2 outcomes of cells continuing to proliferate but being unable to mature in acute myeloid leukaemia (AML)
build up of most immature cells (myeloblasts) in bone marrow with spread into blood; failure of production of normal functioning end cells e.g. neutrophils, monocytes, erythrocytes, platelets, so crowded out (plateles also consumed by intravascular coagulation)
what do mutations in AML usually affect
transcription factors (so transcription of multiple genes is affected)
what does the product of an oncogene prevent (usually acts in dominant manner)
normal function of protein encoded by its normal homologue, disturbing cell behaviour
what to mutations in CML usually affect
gene encoding a protein in signalling pathway between cell surface receptor and nucleus (either membrane receptor or cytoplasmic protein)
CML vs AML: cell kinetics and function
cell kinetics and function not as seriously affected in CML compared to AML
