Cancer 14: Leukemia Flashcards
What is leukemia?
mutation in single lymphoid or myeloid stem cell-or rarelt in common to both
one mutation can be enough-leading to more proliferation, differentiation, survival-take over from norma
can happen in plutipotent heamatopeotic, myeloid stem cell, lymphoid stem cell, or pre B or Pre T cells
can have one hit in early cells-give it some advantage-and they proliferate more-and those advantaged cell can add more mutations-> more aggressive/acute
How does leukemia differ from cancer?
Not a solid tumour-can happen but rare
usually diffuse replacing of nromal bone marrow cells and circulating in blood (overspilling)
also behave different-circulate body and enter tissue
lymphoid cells are used to go around lymphatic system => no concept of invasion and metastasis -benign and malignant have to be distinguished other ways
What are benign and malignant leukemia? What are the ways to categorise leukemias?
Benign-chronic-goes on for long time
malignant-acute-very agressive and can die in weeks
between acute/chronic,
myeloid or lymphoid
B or T
myeloid can be combination of granulocytic, moncytic, erythroid or megakaryotic
How do leukemeias occur?
Can be either due to environement or random chance-still can only explain 10% of them
usually-protooncogenes, creation of fusion/chimeric gene, dysregulation of gene because of translocation putting in under control of other things
loss of tumour supressor genes-usually makes them more agressive
any mutation where lose DNA repair/defective-increase chances
What are the main identifyable causes of leukemia?
Irradiation, anticancer drugs, cigarette smoking, chemicals (like benzene)-
=> aqcuired mutation disease or resulting from somatic mutation
germ cell mutations can be favorable-go back to beneficial, neutral or harmful
What is the difference bwteen acute and chronic myeloid leukemia?
From myeloid lineage (sometimes can mean only granulocytes)
acute-continue to proliferate but not mature-myeloblast accumulate in BM and spread in blood -> occupate BM and failure of production of normal cells –usually TF mutation
increase of lymphoblasts (early lymphoids)
Chronic-often involve signalling protein-not as deep profoud distrubance-just over activated
Increase of production of end cell (mature)-because over activated
increase of differenciated lymphoid cells
so if low in most myeloid-AML
If blood film looks very busy and mature cells-CML
What genes are often involved in AML? and CML?
usually TF-many genes are involved
activating mutations-often dominant and the product prvents function of the normal homologue-big cell changes
Chronic-often involve signalling protein-not as deep profoud distrubance-just over activated–independent of independent signals, apoptosis resitance
What are the symptoms of leukemia and how does it cause it?
accumulation of cells lead to: Leukocytosis, bone pain (acute), hepatomegaly, splenomegaly, lymphadenopathy (lymphoid), thymuc enlargment (t cell), skin infiltration (pappillar lesions, thickenning of skin)
metabolic effects due to cell proliferation-hyperuciceamia-renal failure, weight loss, low grade fever/sweating
Crowding out of normal cells-aneamia, thrombocytopenia, neutropenia -bruises, random heammorhages (like intraventricular)
loss of immune normal function-usually in lymphoid leukemia
What is the epidiemology of acute lymphoblastic leukemia?
not just one disease-many many phenotypes
peak in childhood-under 4. other peak at adult hood, with different genetics (9-22 translocation)
More common B lineage–early exposure protect-may result from delayed exposure to common pathogens
(new town with many different lineages-increase of ALL-new pathogens brought together to people hadnt seen before)
possible link to irradiation in utero, chemicals in utero (ALL rarely results from mutagenic drug)
What are the clinical features of acute lymphblastic leukemia?
Resulting from accumulation
Bone pain, hepatomegaly, spleno megaly, lymphadenopathy, thymic (t cell), testicular enlagment
crowding out of normal cells-fatigue/lethargy, pallor, breathlessness (aneamia)
Fever/infection-neutropenia
Bruising, petechiae, bleeding-thromboctypenia
often cause for young children with bruises
What are the heamotological features of ALL?
Leucoctyosis with lymphoblasts in blood
aneamia( normocytic, normochromic), neutropenia, thrombocytopenia
bone marrow replaced with lymphoblasts
film-non differentiated, mostly one and same cell,
BM film-normally low lymphoblast-just a few and can see stages of differentiations around it. In ALL- MANY lymphoblasts, large-not many differentiated cells around
How do you determine which cell is causing the ALL?
using immunophenotyping-single cell past by laser checked ABs bind to cell Ag (like Cd19, etc)–can determine which cell is B, T, etc
CD19-B cell marker, TdT (marker of immaturity)
also do genetic analysis-look at Chr in general
Hyperdiploidy-good prognosis (extra Chr copies)
Translocation of Chr-poor prognosis
Detemine with FISH-fluoresncent in situ hybridisation (label DNA of interest with probs)
What are the treatments for ALL?
Suppotive-Red cells, platelets, Abx (and anit fungals/viral) –most important tbf
systemic chemotherapy-widespread disease
Intrathecal chemotherapy-lumbar puncture-into spine (or drug that can pass BBB)
treatment much better now–80% childhood survival
