Chronic myelogenous leukemia (CML) is cancer that starts inside bone marrow. This is the soft tissue in the center of bones that helps form all blood cells. CML causes an uncontrolled growth of immature and mature cells that make a certain type of white blood cell called myeloid cells. The diseased cells build up in the bone marrow and blood.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the chronic phase of CML, progression to blast crisis requires other molecular changes. Common secondary abnormalities include mutations in TP53, RB, and p16/INK4A, or overexpression of genes such as EVI1. Additional chromosome translocations are also observed,such as t(3;21)(q26;q22), which generates AML1-EVI1[1].

[1]聽Kyoto Encyclopedia of Genes and Genomes

Chronic myeloid leukemia

Related genes of knockout cell lines
ABL1 AKT1 AKT2 ARAF BAD BAK1
BAX BCR BRAF CCND1 CDK6 CDKN1A
CDKN1B CDKN2A CHUK CRKL GADD45A GADD45B
GRB2 HDAC1 HDAC2 IKBKB IKBKG KRAS
MAP2K1 MAP2K2 MAPK1 MAPK3 MDM2 MYC
NFKB1 NFKBIA NRAS PIK3R1 PIK3R2 PIK3R3
POLK PTPN11 RAF1 RB1 RELA SHC1
SMAD3 STAT5B TGFB1 TGFBR2 TP53