cancer 14 Flashcards
what is leukemia?
- Leukaemia is the cancer of the blood
- Leukaemia results from a series of mutations in a single lymphoid or myeloid stem cell
- These mutations lead the progeny of that cell to show abnormalities in proliferation, differentiation or cell survival
- this leads to the steady expansion of the leukaemic clone, it takes over from normal cells
.what is the epidemiology of leukemia?
- 5% of all cancers are cancers of the blood
- Blood cancers are the most common cancers in men and women aged 15-24 and the main cause of death in 1-34
show which cells might be involved:
Leukemia might affect
- Pluripotent hematopoietic stem cell.
- Myeloid/lymphoid stem cell.
- Pro-/Pre-T/B lymphocyte.
why is leukemia different from other cancers?
- most cancers exist as a solid tumor
- instead, leukemic cells replace the normal bone marrow cells and circulate freely in the bloodstream
- Normal hematopoietic stem cells circulate in the blood and both the stem cells and the cells derived from them can enter tissues, and normal lymphoid stem cells recirculate between tissues and blood.
how do normal hematopoietic stem cells and lymphoid stem cells circulate?
- Normal haematopoietic stem cells circulate in the blood and both the stem cells and the cells derived from them can enter tissues
- normal lymphoid stem cells recirculate between tissues and blood.
can the terms of invasion and metastasis be applied?
can the words benign and malignant be used?
- they cannot as blood cells always travel around the body
- Benign leukaemia = chronic
- Malignant = acute (aggressive and quick death)
How is leukemia classified?
- Leukemia can be acute or chronic
- it can also be lymphoid or myeloid
- Lymphoid can be B or T lineage
- Myeloid can be any combination of granulocytic, monocytic, erythroid or megakaryocytic
what are the final 4 classes of leukemia?
- ALL – Acute Lymphoblastic Leukaemia
- CLL – Chronic Lymphocytic Leukaemia.
- AML – Acute Myeloid Leukaemia.
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why does leukemia occur?
- Leukemia is an acquired genetic disease arising from somatic mutation
- Leukemia results from a series of mutations in a single stem cell
- Some mutations result from identifiable or unidentifiable oncogenic influences
- others are random errors that accumulate over time
what are the improtant leukaemogenic mutations ?
- Mutation in a known proto-oncogene - Creation of a novel gene, e.g. a chimaeric or fusion gene - Dysregulation of a gene when translocation brings it under the influence of the promoter or enhancer of another gene - Loss of function of a tumour-suppressor gene resulting from a deletion or mutation of gene, this makes a leukaemia more aggressive - If there is a tendency to increased chromosomal breaks, the likelihood of leukaemia is increased - if the normal repair mechanism is affected then the likelihood of leukaemia is increased
- which genetic conditions increase the likelihood of leukemia?
- Down’s syndrome Chromosomal fragility syndromes Defects in DNA repair Inherited defects of tumour-suppressor genes
what environmental factors contribute to leukaemia?
Irradiation
Anti-cancer drugs
Cigarette smoking
Chemicals—benzene
what kind of mutation causes leukemia?
- results from somatic mutation - Mutation in germ cells may bring favourable, neutral or unfavourable characteristics to the species - if negative then might cause leukaemia
what does myeloid mean?
myeloid = overall generic term
blood cells that arise from a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets
what is the nature of acute myeloid leukemia?
- in acute myeloid leukemia cells continue to proliferate but they no longer mature so there is a build up of the most immature cells
- Failure of production of normal functioning end cells such as neutrophils, monocytes, erythrocytes, platelets
- the mutations often affect the transcription factors so transcription of genes is affected
what happens to the platelets?
- the platelets are consumed within the bloodstream
what is the nature of chronic myeloid leukemia?
- Responsible mutations usually affect genes encoding proteins involved in signaling pathways from the receptors
- Cell kinetics & function are not as seriously affected as in AML
- But there is still reduced apoptosis and the cell progressively expands in population.
AML vs CML production of end cells?
- AML = failure of production of end cells
- CML = increased production of end cells
What is the difference between acute and chronic lymphoid leukemias?
- acute lymphoid leukemias is an increase in very immature cells with failure to develop into T and B cells
- In chronic lymphoid leukemias, the leukemic cells are mature although abnormal T and B cells
what are the disease characteristics of leukemia?
due to the accumulation of abnormal cells
metabolic effects
crowding of normal cells
the accumulation of abnormal cells leads to :
- Leucocytosis
- bone pain
- hepatomegaly (abnormal enlargement of the liver)
- splenomegaly (abnormal enlargement of the spleen)
- lymphadenopathy (abnormally sized lymph nodes) (if lymphoid)
- thymic enlargement
- skin infiltration
what are the metabolic effects of Leukaemic cell proliferation lead to:
- Hyperuricemia and renal failure
- weight loss
- low-grade pyrexia (high tempreature)
- hidrosis (sweating)
Crowding out of normal cells leads to:
- anemia
- neutropenia
- thrombocytopenia.
show the skin of a patient with AML
- papular lesions
- thickening of skin
- bruises
who does Acute lymphoblastic leukaemia affect?
children
why do some children develop ALL?
factors that give protection?
- ALL is largely a disease of children the highest incidence is at age 4
- Factors that protect from ALL:
early exposure to pathogens protects from leukemia
larger families relate to less leukemia
socio-economic class
early social interactions
enterovirus infection gave protection
what might cause leukaemia in children?
- radiation in utero might cause leukaemia
- Epstein–Barr virus infection
- In utero exposure to certain chemicals Baygon ? Dipyrone?
what are the clinical features of acute lymphoblastic leukemia stemming from ?
- Bone pain
- Hepatomegaly
- Splenomegaly
- Lymphadenopathy
- Thymic enlargement
- Testicular enlargement
what are the clinical features of acute lymphoblastic leukemia that stem from the crowding out of normal cells?
Fatigue, lethargy, pallor, breathlessness (caused by anaemia) Fever and other features of infection (caused by neutropenia) Bruising, petechiae (pinpoint haemorrhages, bleeding (caused by thrombocytopenia)
what are the hematological features of ALL?
- Leucocytosis with lymphoblasts in the blood
- Anemia (normocytic, normochromic)
- Neutropenia
- Thrombocytopenia
- Replacement of normal bone marrow cells by lymphoblasts
- low platelet count
what are the investigations carried out for ALL?
- FBC with liver and renal function tests.
- Bone marrow aspirate.
- molecular analysis
- Immunophenotyping
- all of these are good for looking at the prognosis of ALL
- eg. Hyperdiploidy (many extra chromosomes) means good prognosis.
show a blood film of a patient with acute lymphoblastic leukemia?
- lots of lymphoblasts - complete lack of platelets
what is immunophenotyping?
- looking at the lineaging of the cell
- pass cells through a laser beam detector picking up fluorescence due to antibody being bound to an antigen leukemic cells expressing CD10 and expressing terminal deoxynucleotidalnucelase (shows immaturity)
what is cytogenetic analysis?
- gives information about prognosis
show pic of reciprocal transformation
4 and 11 have undergone reciprocal transformation
- this is leukemogeneic
this suggests poor prognosis
how can we detect fusion cells?
- This can be detected by two fluorescent probes
- the method is called fluorescence in situ hybridization —FISH
how do we treat Acute lymphoblastic leukemia?
Treatment types include:
- Supportive
- Systemic chemotherapy.
- Intrathecal chemotherapy.
much of treatment is supportive
Red cells
Platelets (eg for hemorrhage)
Antibiotics
lots of the drugs don’t cross the blood-brain barrier so we need to use lumbar punctures
how has survival of Acute lymphoblastic leukaemia changed?
- it has increased
- more people die of side effects rather than the actual tumor
