KEGG   PATHWAY: mmu05220Help
Entry
mmu05220                    Pathway                                

Name
Chronic myeloid leukemia - Mus musculus (mouse)
Description
Chronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and other hematopoetic cell lineages are involved in the process of clonal proliferation and differentiation. 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.
Class
Human Diseases; Cancers
BRITE hierarchy
Pathway map
Chronic myeloid leukemia
mmu05220

All organismsOrtholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
110279  
Bcr; breakpoint cluster region [KO:K08878] [EC:2.7.11.1]
11350  
Abl1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
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]
12402  
Cbl; Casitas B-lineage lymphoma [KO:K04707] [EC:2.3.2.27]
208650  
Cblb; Casitas B-lineage lymphoma b [KO:K04707] [EC:2.3.2.27]
80794  
Cblc; Casitas B-lineage lymphoma c [KO:K04707] [EC:2.3.2.27]
30955  
Pik3cg; phosphoinositide-3-kinase, catalytic, gamma polypeptide [KO:K00922] [EC:2.7.1.153]
18706  
Pik3ca; phosphatidylinositol 3-kinase, catalytic, alpha polypeptide [KO:K00922] [EC:2.7.1.153]
18707  
Pik3cd; phosphatidylinositol 3-kinase catalytic delta polypeptide [KO:K00922] [EC:2.7.1.153]
74769  
Pik3cb; phosphatidylinositol 3-kinase, catalytic, beta polypeptide [KO:K00922] [EC:2.7.1.153]
18709  
Pik3r2; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 (p85 beta) [KO:K02649]
18708  
Pik3r1; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) [KO:K02649]
320207  
Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5, p101 [KO:K02649]
18710  
Pik3r3; phosphatidylinositol 3 kinase, regulatory subunit, polypeptide 3 (p55) [KO:K02649]
11651  
Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  
Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  
Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
12015  
Bad; BCL2-associated agonist of cell death [KO:K02158]
12048  
Bcl2l1; BCL2-like 1 [KO:K04570]
12675  
Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  
Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
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]
17246  
Mdm2; transformed mouse 3T3 cell double minute 2 [KO:K06643] [EC:2.3.2.27]
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]
19247  
Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
20662  
Sos1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
20663  
Sos2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
15461  
Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  
Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  
Nras; neuroblastoma ras oncogene [KO:K07828]
110157  
Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
11836  
Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
109880  
Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
26395  
Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  
Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  
Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  
Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
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]
17869  
Myc; myelocytomatosis oncogene [KO:K04377]
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]
12443  
Ccnd1; cyclin D1 [KO:K04503]
12567  
Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
12571  
Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
19645  
Rb1; retinoblastoma 1 [KO:K06618]
13555  
E2f1; E2F transcription factor 1 [KO:K17454]
242705  
E2f2; E2F transcription factor 2 [KO:K09389]
13557  
E2f3; E2F transcription factor 3 [KO:K06620]
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]
21812  
Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:2.7.11.30]
21813  
Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:2.7.11.30]
17128  
Smad4; SMAD family member 4 [KO:K04501]
14013  
Mecom; MDS1 and EVI1 complex locus [KO:K04462]
12394  
Runx1; runt related transcription factor 1 [KO:K08367]
13016  
Ctbp1; C-terminal binding protein 1 [KO:K04496]
13017  
Ctbp2; C-terminal binding protein 2 [KO:K04496]
15182  
Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
433759  
Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
17127  
Smad3; SMAD family member 3 [KO:K04500]
Compound
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Ren R.
  Title
Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia.
  Journal
Nat Rev Cancer 5:172-83 (2005)
Reference
  Authors
Deininger MW, Goldman JM, Melo JV.
  Title
The molecular biology of chronic myeloid leukemia.
  Journal
Blood 96:3343-56 (2000)
Reference
  Authors
Calabretta B, Perrotti D.
  Title
The biology of CML blast crisis.
  Journal
Blood 103:4010-22 (2004)
Reference
  Authors
Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM.
  Title
The biology of chronic myeloid leukemia.
  Journal
N Engl J Med 341:164-72 (1999)
Reference
  Authors
Mitani K.
  Title
Molecular mechanisms of leukemogenesis by AML1/EVI-1.
  Journal
Oncogene 23:4263-9 (2004)
Reference
  Authors
Dong M, Blobe GC.
  Title
Role of transforming growth factor-beta in hematologic malignancies.
  Journal
Blood 107:4589-96 (2006)
Reference
PMID:9834202
  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
  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
  Authors
Baldwin AS.
  Title
Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB.
  Journal
J Clin Invest 107:241-6 (2001)
Reference
  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
Nat Med 8:1145-52 (2002)
Reference
  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
Nat Chem Biol 8:285-93 (2012)
KO pathway
 

DBGET integrated database retrieval system