A woman in her late sixty's complaining from laziness, sore throat and severs mouth ulcers. Under the GP clinical examination, she was diagnosed with moderate pallor, splenomegaly, fever and lymphomegaly. Also she suffered from bleeding ulcers. A blood sample was taking from the patient for testing. The blood cell count as well as the differential count were investigated and discussed, where it has been found that patient A to be suffering from acute myeloid leukaemia (AML). The diagnosis was confirmed due to the following findings;
The above two tables (1 and 2) shows some abnormal results from the carried tests, from there the diagnosis was made for the 67 year old patient. Table 1 illustrates the abnormal results of the blood count. The patient had a very elevated amount of WBC. WBC contains five different types of cells, each having specific function to provide a strong protection system against illnesses and foreign molecules in the individuals body. A high level of these leukocytes is a problem but not a disease and known as leukocytosis. However, it's mostly linked to infections or white blood cells tumour such as leukaemia. Therefore, further test is needed to demonstrate the increased type of cells and disease. RBC's count is shown low, which in turn has also effected the HGB concentration of the blood. This explains the feeling of weakness and pallor in the patient as a reduced RBC is associated with anaemia. The patient had hypertrophic bleeding gum due to the PLT count being low which has lead to uncontrolled bleeding. This can be due to splenomegaly or a fault in the BM where it does not produce enough platelets to maintain clotting; this is known as thrombocytopenia. Table 2 demonstrate a high reduction of neutrophil count, which lead to a great elevation of the large unstained cells (LUC) as well as monocytes. LUC were identified as cells that are larger in size than lymphocytes and peroxidise negative blasts. When the numbers of neutrophils are decreased in the individual, it can be associated with aplastic anemia, drug-induced neutropenia. High count of monocytes pinpoint to infection caused by bacterial pathogen. While low level of eosinophils is linked to acute and chronic inflammation, stress or drugs such as steroids.
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Blood film was also done; this is to examine the morphology of the cells microscopically. The blood film at this case should be stained to a high quality for better determination. Additional cytochemical stains are also required to detect and confirm cell type, origin and other pattern for the study of blast cells and lymphocytes and to distinguish the subtypes of the leukaemia's.
Figure 1: Blood film of Patient E
Granulocytopenia, thrombocytopenia, and/or anaemia, with or without leukocytosis are the hallmarks of acute myeloid leukaemia (AML).
AML is heterogeneous disease that is a type of cancer effecting white blood cells (WBC) and bone marrow (BM). This disease is caused due to multiple genetic defects including more than 160 chromosomal abnormalities, such as the translocation of chromosomes that involves oncogenes and transcription factors, receptor alteration of the growth factors, as well as activating the signal for the transduction pathway (Appelbaum, et al, 2001). AML is characterised of the rapidly growth of cells that are incomplete of maturity, and is divided into eight different subclasses according to the cell morphology, phenotype and histochemistry named M0 to M7 (table 3). This classification is known as the FAB system (French-American-British), (Hann, et al, 2006).
Table 3: AML classification by FAB criteria, and their cytogenetic association.
Myeloblastic leukaemia without maturation
Myeloblastic leukaemia with maturation
Acute hypergranular promyelocytic leukemia
Acute myelomonocytic leukaemia
inv(16)(p13q22), t(16;16), del(16q)
Acute monoplastic leukaemia
del (11q), t(9;11), t(11;19)
Acute megaryoblastic leukaemia
Table adapted from pediatric haematology by Hann et al, (2006)
The blood film of the patient shows myeloblasts/monoblast, promonocytes and <30% monocytes. More than 20% of the cells are non-erythroid. Auer rods were not detected however; this is a common finding in AML. Also the cytochemistry of the cells defined the subtype of the AML which is to be Acute Myelomonocytic Leukaemia (M4), but due to the high number of promonocytes and monocytes the case was classified as AML with maturation (M2).
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The molecular mechanism of AML that results in the incomplete maturation of the cells involves many defects and mutations. However in most cases chromosomal translocations which activate abnormal genes are the mostly observed. This fault may result in the rapid proliferation of the cells from BM, as well as the reduction of apoptosis (cell death process). When AML1 is combined with the CBFβ it produces transcriptional factors that act as a regulator in genes that are associated with cell differentiation and myelogenesis processes. However, in AML-M2 these transcriptional factors are disrupted leading to arrest cell differentiation. For example, the translocation between chromosome 8 and 21 in the long arm 22 involve the fusion of RUNX1 with the transcriptional repressor RUNX1T1. This is a balanced translocation. In the normal event this translocation t(8;21) result in the production of a fusion gene that allows differentiation of the cells. However in AML when RUNX1-RUNX1T1 binds to the CBF binding site, the maturation and differentiation of cells are then inhibited, as well as the reduction of apoptosis due to the activation of the anti-apoptosis gene BCL-2.