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Myeloid malignancies are divided into 3 categories:Disorders of proliferationChronic myeloid leukemiaMyeloproliferative disordersDisorders of differentiationMyelodysplastic syndromesDisorders of differentiation and proliferationAcute myeloid leukemia Chronic myeloid leukemia is a disorder of proliferation → it is a stem cell disease.= A 48-year-old male patient suffers from fatigue, but has no other complaints. Physical examination shows pallor and an enlarged spleen. A laboratory test shows:Hb: 8,0 mmol/L → too lowMCV (mean corpuscular volume): 96 fLLeukocytes: 113 x 10E9/L → too highPlatelets: 154 x 10E9/L → normalLeukocyte differentiation shows:1 promyelocytes10 myelocytes8 metamyelocytes8 band forms53 segmented neutrophilsThere shouldn’t be any promyelocytes, myelocytes and metamyelocytes present in the blood. The only cells that should be present are mature blood cells. The diagnosis is Philadelphia chromosome positive chronic myeloid leukemia (CML). The driver mutation of CML is BCR/ABL, caused by a translocation of chromosome 9 and 22. This mutation causes cells to have a proliferative advantage. There is no mutation in differentiation genes → differentiation in mature stages is normal. Therefore, neutrophils are segmented as usual. Chromosome 9 contains the ABL gene, chromosome 22 contains the BCR gene. The mutation takes place as follows:Both chromosomes breakThe ABL gene attaches to the BCR gene on chromosome 22 → the Philadelphia chromosome is createdA constantly active tyrosine kinase is madeMultiple substrates are phosphorylated → multiple ways of absent regulation are madeChronic myeloid leukemia arisesIt is unknown why the translocation of chromosome 9 and 22 occurs. There is no relation with exposition to...
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