Flashcards in Leukaemia Deck (19)
Haematopoietic process of a neutrophil
1. Myeloblast in bone marrow
2. Promyelocyte ---> Myelocyte
3. Metamyelocyte ----> Band neutrophil
4. Neutrophil forms in bone marrow that migrates into the blood.
Haematopoietic process of a macrophage
1. Starts off as a myeloblast in the bone marrow, a unipotent stem cell.
2. Myeloblast ---> Promonocyte.
3. Promonocyte ---> Monocyte in the blood
4. Monocyte---> immature macrophage in tissues.
5. Immature macrophage---> Mature macrophage
Granulocyte colony-stimulating factor
Signally, glycoprotein molecule that stimulates neutrophil proliferation and maturation.
Granulocyte-macrophage colony stimulating factor.
Stimulates the proliferation and maturation of neutrophils, macrophages and eosinophils.
5 methods of genetic mutations that can cause cancer
1. Point mutation- change of one nucleotide to another.
2. Translocation- rearrangement of parts between nonhomologous chromosomes.
3. Partial chromosomal deletion.
4. Chromosomal duplication.
5. DNA methylation or deacylation of histones.
Clonal evolution of AML
The change from proto-oncogene to oncogene which increases the change of cells becoming malignant.
Stimulation of oncogenes and inhibition of tumour suppressor gene causes XS proliferation and failure of apoptosis.
Chemicals, radiation, drugs, viruses and mutations trigger the incidence of malignant cells.
Clinical features of AML
Myelofibrosis- bone marrow cancer
Thrombocythemia- excess platelets
Blood condition shown in those with myelofibrosis
Due to lesions in the bone marrow, there is an increase in immature granulocytes and RBCs.
JAK-STAT signalling for AML
1. Acquired abnormality in the bone marrow causes:
Excess red cell precursors
2. 95% of red cells with mutated JAK-2 receptors develop into polycythaemia vera.
3. 50% of megakaryocytes have mutated JAK-2 receptors. This develops into thrombocythaemia.
4. Thrombocythemia and polycythaemia vera can develop into primary myelofibrosis.
5. Primary myelofibrosis and polycythaemia vera can develop into AML.
Mutation of JAK2 receptor for megakaryocytes or red cell precursors which enhances proliferative downstream signalling in excess.
Stimulates polycythaemia and thrombocythemia.
Management of AML
This prevents the excess proliferative, cell division of megakaryocytes and red cell precursors.
It does this by suppressing the production of granulocytes in the bone marrow.
Chronic myeloid leukaemia
Cancer of the WBCs where there is unregulated growth of myeloid in the bone marrow which is pushed out into cells.
This causes a great number of mature granulocytes and their precursors to be found in the blood.
This cancer is caused by the Philadelphia chromosome
A translocation mutation associated with CML.
Chromosome 22 is abnormally short as part of it translocated to chromosome 9.
This causes the BCR on chromosome 22 to be attached to ABL1 gene on chromosome 9.
This BCR-ABL1 formation creates an oncogene- a tyrosine kinase signalling protein.
The tyrosine kinase protein is always on which phosphorylates other proteins and stimulates further proliferation of cells
FISH for BCR-ABL1
Fluorescence in situ hybridisation is a sensitive test that identifies BCR-ABL1 hybrid.
BCR on chromosome 22 is coloured with green light.
ABL1 on chromosome 9 is coloured with red.
When BCR-ABL1 hybridisation is present, there will be yellow light (green + red light).
Medication used to treat ALL and CML.
Both chromosomes have Philadelphia chromosomes.
Imatinib competitively competes with substrate on BCR-ABL1 tyrosine kinase.
This prevents the substrate from being phosphorylated and proliferating the tumour cell.
Treatment of AML
Chemotherapy- combination of drugs and myeloablative cycles of treatment- suppresses bone marrow activity.
Antibiotics, antifungals- due to extremely immunosuppressed state.
Transfusion of blood and platelets- due to suppression of bone marrow
Stem cell transplantation- autograft or allograft.
Drug that prevents the formation of deoxyribonucleotides.
This suppresses proliferation of cells in the bone marrow.
Medical emergency that has a high risk of death.
Occurs when there is any extremely low neutrophil cell count in the blood.
Infections from gram negative bacteria causes the most damage