Diagram showing the cells where<unk>  develops. The malignant cell in<unk>  is the myeloblast. In normal development of blood cells (hematopoiesis), the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will mature into a white blood cell such as an eosinophil, basophil, neutrophil or monocyte. In<unk> , though, a single myeloblast accumulates genetic changes which stop maturation, increase its proliferation, and protect it from programmed cell death (apoptosis). Much of the diversity and heterogeneity of<unk>  is because leukemic transformation can occur at a number of different steps along the differentiation pathway. Genetic abnormalities or the stage at which differentiation was halted form part of modern classification systems. Specific cytogenetic abnormalities can be found in many people with<unk> ; the types of chromosomal abnormalities often have prognostic significance. The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the "differentiation arrest". For example, in APL, the t(15;17) translocation produces a PML-RARA fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation. The clinical signs and symptoms of<unk>  result from the growth of leukemic clone cells, which tends to interfere with the development of normal blood cells in the bone marrow. This leads to neutropenia, anemia, and thrombocytopenia. Other symptoms can arise from the infltration of malignant cells into parts of the body, such as the gingiva and skin. Many cells develop mutations in genes that affect epigenetics, such as DNA methylation. When these mutations occur, it is likely in the early stages of<unk> . Such mutations include in the DNA demethylase TET2 and the metabolic enzymes IDH1 and IDH2, which lead to the generation of a novel oncometabolite, D-2-hydroxyglutarate, which inhibits the activity of epigenetic enzymes such as TET2. Epigenetic mutations may lead to the silencing of tumor suppressor genes and/or the activation of proto-oncogenes.
Acute myeloid leukemia
Acute lymphoblastic leukemia
Myeloid leukemia
Lymphoid leukemia
Prolymphocytic leukemia
Acute monocytic leukemia
Leukemoid reaction
T-cell leukemia