Entry |
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Name |
Chronic myeloid leukemia - Mus musculus (mouse)
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Description |
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.
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Class |
Human Diseases; Cancer: specific types
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Pathway map |

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Organism |
Mus musculus (mouse) [GN: mmu]
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Gene |
12928 | Crk; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438] |
12929 | Crkl; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438] |
18706 | Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
18707 | Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
74769 | Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
18709 | Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
18708 | Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
18710 | Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
12015 | Bad; BCL2-associated agonist of cell death [KO:K02158] |
16151 | Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210] |
18035 | Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734] |
18033 | Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580] |
19697 | Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735] |
22059 | Trp53; transformation related protein 53 [KO:K04451] |
12576 | Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624] |
14784 | Grb2; growth factor receptor bound protein 2 [KO:K04364] |
14389 | Gab2; growth factor receptor bound protein 2-associated protein 2 [KO:K08091] |
20662 | Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099] |
20663 | Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099] |
15461 | Hras; Harvey rat sarcoma virus oncogene [KO:K02833] |
16653 | Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827] |
20416 | Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279] |
216148 | Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447] |
20418 | Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448] |
271849 | Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449] |
20850 | Stat5a; signal transducer and activator of transcription 5A [KO:K11223] |
20851 | Stat5b; signal transducer and activator of transcription 5B [KO:K11224] |
12578 | Cdkn2a; cyclin dependent kinase inhibitor 2A [KO:K06621] |
12575 | Cdkn1a; cyclin-dependent kinase inhibitor 1A (P21) [KO:K06625] |
19645 | Rb1; RB transcriptional corepressor 1 [KO:K06618] |
13197 | Gadd45a; growth arrest and DNA-damage-inducible 45 alpha [KO:K04402] |
17873 | Gadd45b; growth arrest and DNA-damage-inducible 45 beta [KO:K04402] |
23882 | Gadd45g; growth arrest and DNA-damage-inducible 45 gamma [KO:K04402] |
107986 | Ddb2; damage specific DNA binding protein 2 [KO:K10140] |
21803 | Tgfb1; transforming growth factor, beta 1 [KO:K13375] |
21808 | Tgfb2; transforming growth factor, beta 2 [KO:K13376] |
21809 | Tgfb3; transforming growth factor, beta 3 [KO:K13377] |
12394 | Runx1; runt related transcription factor 1 [KO:K08367] |
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Compound |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Ren R. |
Title |
Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. |
Journal |
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Reference |
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Authors |
Deininger MW, Goldman JM, Melo JV. |
Title |
The molecular biology of chronic myeloid leukemia. |
Journal |
Blood 96:3343-56 (2000) |
Reference |
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Authors |
Calabretta B, Perrotti D. |
Title |
The biology of CML blast crisis. |
Journal |
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Reference |
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Authors |
Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM. |
Title |
The biology of chronic myeloid leukemia. |
Journal |
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Reference |
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Authors |
Mitani K. |
Title |
Molecular mechanisms of leukemogenesis by AML1/EVI-1. |
Journal |
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Reference |
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Authors |
Dong M, Blobe GC. |
Title |
Role of transforming growth factor-beta in hematologic malignancies. |
Journal |
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Reference |
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Authors |
Kurokawa M, Mitani K, Imai Y, Ogawa S, Yazaki Y, Hirai H. |
Title |
The t(3;21) fusion product, AML1/Evi-1, interacts with Smad3 and blocks transforming growth factor-beta-mediated growth inhibition of myeloid cells. |
Journal |
Blood 92:4003-12 (1998) |
Reference |
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Authors |
Brusa G, Benvenuti M, Mazzacurati L, Mancini M, Pattacini L, Martinelli G, Barbieri E, Greenberger JS, Baccarani M, Santucci MA. |
Title |
p53 loss of function enhances genomic instability and accelerates clonal evolution of murine myeloid progenitors expressing the p(210)BCR-ABL tyrosine kinase. |
Journal |
Haematologica 88:622-30 (2003) |
Reference |
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Authors |
Baldwin AS. |
Title |
Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. |
Journal |
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Reference |
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Authors |
Shin I, Yakes FM, Rojo F, Shin NY, Bakin AV, Baselga J, Arteaga CL. |
Title |
PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. |
Journal |
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Reference |
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Authors |
Hantschel O, Warsch W, Eckelhart E, Kaupe I, Grebien F, Wagner KU, Superti-Furga G, Sexl V |
Title |
BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia. |
Journal |
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Related pathway |
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KO pathway |
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