Chronic myeloid leukemia
| PAG Title | Chronic myeloid leukemia |
| PAG ID | WIG000495 |
| Type | P |
| Source Link |  MSigDB |
| Publication Reference | NA |
| PAG Description | Chronic myelogenous leukaemia (CML) is a biphasic disease, initiated by expression of the BCR/ABL fusion gene product in self-renewing, haematopoietic stem cells (HSCs). HSCs can differentiate into common myeloid progenitors (CMPs), which then differentiate into granulocyte/macrophage progenitors (GMPs). HSCs can also differentiate into common lymphoid progenitors (CLPs), which are the progenitors of lymphocytes such as T cells and B cells. The initial chronic phase of CML (CML-CP) is characterized by a massive expansion of the granulocytic-cell series. Acquisition of additional genetic mutations beyond expression of BCR/ABL causes the progression of CML from chronic phase to blast phase (CML-BP), characterized by an accumulation of myeloid or lymphoid blast cells. The BCR/ABL fusion gene encodes p210BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. The tyrosine kinase activity is essential for cell transformation and the cytoplasmic localization of BCR/ABL allows the assembly of phosphorylated substrates in multiprotein complexes that transmit mitogenic and antiapoptotic signals. Additional cytogenetic and molecular changes are frequently found in patients with CML during the progression of the disease from chronic to blast phase. Some of the genetic changes include mutations in TP53, RB, and CDKN2A (also known as p16INK4A), or overexpression of genes such as EVI1. Additional chromosome translocations are also observed, such as t(3;21)(q26;q22), which generates AML1/EVI1. AML1/EVI-1 represses TGF-beta-mediated growth inhibitory signal. |
| Species | Homo sapiens |
| Quality Metric Scores | nCoCo Score: 4,316 |
| Information Content | Rich |
| Other IDs | M321 |
| Base PAG ID | WIG000495 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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