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Haemopoiesis is the production of cellular blood components which are derived from haematopoietic stem cells (HSC).HSC are usually found in the medulla of the bone, otherwise known as the bone marrow and can give rise to all different mature blood cell types. The HSC has the ability to stop their cells from becoming depleted as are self renewing because when they proliferate, some of their daughter cells stays as HSC's.
The symptoms of acute leukaemia tend to develop very suddenly as opposed to the progression of symptoms over time in chronic leukaemia. The symptoms include anemia which is usually from a result of a reduction in the red blood cell (RBC) count. Anemia cause further problems such as paleness, fatigue, and shortness of breath. Thrombocytopenia also develops as there are reduced numbers in platelets in the circulating system. This can cause excess bleeding at the site of injury even if its from a minor trauma as the clotting platelets in the blood are not enough. In many cases sufferers may experience fevers, epistaxis, petechiae, bone and joint pain and frequent infections due to the reduction of infection-fighting WBC in the blood. There may also be enlargement of the liver and spleen (hepatosplenomegaly) and enlargement of lymph nodes (lymphadenopathy).
The blood film would show cell with big nucleus that fill almost all of the cell, leaving very little cytoplasm. The cells are swollen and tend to clump up with each other. There is a presence of auer rods. There is more than 20% of myeloblasts, high levels of leucocytes (135.3 x 109/L. low RBC counts and cells contains no granules. (199 words)
State the typical manifestation of someone presenting with chronic leukaemia including the blood film morphology. (word limit: 200 words) (5 marks)
Chronic leukaemia tends to develop slowing over a long period of time ranging from many months to years without being noticed. Symptoms include swelling of the spleen, liver and lymph nodes. There is also an increase in the amount of WBC. Anemia also occurs because of the reduced number of RBC. They have fevers, weight loss, and tendency to bruise and bleed easily.
The blood film morphology usually shows that in CML leucocytosis is over 100,000/mm3 in the WBC. There are leukocytes that have eosinophils and basophils and neutrophil precursors.
In CLL it shows reduced numbers of RBC and platelets. Lymphocytosis is 5000 mm3. Lymphocytes are small and normal with around 50% of them n the blood film showing abnormalities such as condensed chromosomes in a round nuclei.
Explain the following techniques and give one example for each, of application and diagnosis or monitoring of leukaemia: (word limit: 230) (15 marks)
Cytochemistry: this uses Myeloperoxidase (MPO) staining which stains and identifies cells and their composition. It helps to recognize ALL from AML.
Immunophenotyping: this uses flow cytometric Immunophenotyping to sort out T-lymphocytes by their CD antigens with the aid of fluorescence/ laser lights to establish where there is overpopulation in immunophenotypic marker types. It's also used to analyze heterozygous populations of cells in respect to their state of differentiation and biological lineage (presence and absence of some membrane structures).
Cytogenetics: this is done by fluorescent in situ hybridization (FISH) technique. It assesses chromosomal abnormalities that are related to leukaemia. It diagnoses and tells what specific type of leukaemia it is. It recognizes translocations for chronic myelocytic leukaemia (9;22), acute myelocytic leukaemia (8;21). Deletions associated with myelodysplastic syndromes or AML (5q;7q)and finally trisomies (trisomy 12) for CML. FISH diagnose leukaemias that look similar but does not share genetic abnormalities and require different treatments. (154 Words)
What is the Philadelphia chromosome? Give an example of where it is commonly found. (word limit: 120 words) (5 marks)
Philadelphia chromosome is where chromosome 22 has an abnormality due to part of chromosome 9 being translocated onto it. This occurs in single bone marrow cells that causes chronic myeloid leukaemia (CML) and is also found in acute lymphoblastic leukaemia. The translocation is causes by a process known as clonal expansion where many cells are being produced from the one mutant cell. The Philadelphia chromosome carries the fusion gene BCR-ABL which is derived from proto-oncogene ABL from chromosome 9 and BCR proto-oncogene from chromosome 22.
Fig 1: the formation of the Philadelphia chromosome.
State the difference between stem cell and bone marrow transplants. (word limit: 100 words) (4marks)
Stem cells transplant is when stem cells are acquired by apheresis from the peripheral blood and can be done conveniently at the outpatient department. The apheresis process filters any unwanted blood elements so that only stem cells are collected. However, bone marrow transplant is when stem cells are harvested directly from the bone marrow using fine needle. This is usually taken from around the hip joint, under general anesthesia and requires hospitalization. The collection of stem cells from the bone marrow is much richer in stem cells that that collected by apheresis in the circulating blood. (96 words)
State the difference between autologous and allogenic transplants. (word limit: 50 words) (4 marks)
Autologous transplants is when stem cells are collected from the patient's own body (weather from blood or bone marrow) and the ones collected should not be contaminated with cancer meanwhile allogenic transplant is when stem cells are recovered from a donor that matches the recipient at histocompatibility antigens. (48 words)