“Cancer of myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production”.
Incidence:
- Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults and becomes increasingly common with age, with a median onset of 65 years.
- It forms only a minor fraction (10–15%) of the leukaemias in childhood.
- Cytogenetic abnormalities and response to initial treatment have a major influence on prognosis.
Pathogenesis:
- Mutations in the gene encoding transcription factors that are req for normal myeloid cell differentiation.
- These mutations interfere with the differentiation of early myeloid cells, leading to accumulation of myeloid precursors (blasts) in the marrow.
- t(15;17) in acute promyelocytic leukemia, which results in fusion of the retinoic acid receptor α (RARA) gene on chromosome 17 and PML gene on chromosome 15.
- This produces PML/RARA fusion protein, that blocks myeloid differentiation.
Clinical Features:
The clinical features of AML are dominated by the pattern of bone marrow failure
caused by the accumulation of malignant cells within marrow.
- Infections are frequent, and anaemia and thrombocytopenia are often profound.
- A bleeding tendency caused by thrombocytopenia and disseminated intravascular coagulation (DIC) is characteristic of the promyelocytic variant of AML.
- Tumour cells can infiltrate a variety of tissues. Gum hypertrophy and infiltration, skin involvement and CNS disease are characteristic of the myelomonocytic and monocytic subtypes.
Lab Diagnosis:
Hematological investigations:
- Haematological investigations reveal a normochromic normocytic anaemia with thrombocytopenia in most cases.
- The total white cell count is usually increased.
Blood film: - Blood film examination typically shows a variable numbers of blast cells.
Bone marrow:
- The bone marrow is hypercellular and typically contains many leukaemic blasts.
- Blast cells are characterized by morphology, immunological (flow cytometric) cytogenetic and molecular genetic analysis for confirming the diagnosis, determining prognosis and developing a treatment plan.
Myeloblasts:
- Precursors of granulocytes.
- Have delicate nuclear chromatin, three to five nucleoli, and fine azurophilic cytoplasmic granules.
- Have Auer rods (distinctive red staining rod-like structures).
- Auer rods particularly numerous in acute promyelocytic leukemia, and are specific for neoplastic myeloblasts and thus a helpful diagnostic clue when present.
Cytochemistry is no longer used in most centres.
Tests for DIC:
- Often positive in patients with the promyelocytic variant of AML.
Biochemical tests:
- Biochemical tests arperformed as a baseline before treatment begins and may reveal raised uric acid or lactate dehydrogenase.
Immunophenotype:
- Myeloid associated antigens, such as CD13, CD14, CD15, CD64, CD117.
- Such markers are helpful in distinguishing AML from ALL.
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