KEGG   DISEASE: Chronic myeloid leukemia
H00004                      Disease                                

Chronic myeloid leukemia
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.
Human diseases [BR:br08402]
  Cancers of haematopoietic and lymphoid tissues
   H00004  Chronic myeloid leukemia
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Neoplasms of haematopoietic or lymphoid tissues
   Myeloproliferative neoplasms
    2A20  Non mast cell myeloproliferative neoplasms
     H00004  Chronic myeloid leukemia
Cancer-associated carbohydrates [br08441.html]
hsa05220  Chronic myeloid leukemia
nt06276  Chronic myeloid leukemia
N00002  BCR-ABL fusion kinase to RAS-ERK signaling pathway
N00048  BCR-ABL fusion kinase to PI3K signaling pathway
N00055  BCR-ABL fusion kinase to Jak-STAT signaling pathway
N00067  Deleted p14(ARF) to p21-cell cycle G1/S
N00070  Mutation-inactivated p16(INK4a) to p16-cell cycle G1/S
N00074  Loss of RB1 to cell cycle G1/S
N00106  AML1-EVI1 fusion to TGF-beta signaling pathway
N00107  EVI-1 overexpression to TGF-beta signaling pathway
N00115  Mutation-inactivated TP53 to transcription
BCR-ABL (translocation) [HSA:25] [KO:K06619]
EVI1 (overexpression) [HSA:2122] [KO:K04462]
AML1 (translocation) [HSA:861] [KO:K08367]
p16/INK4A (mutation) [HSA:1029] [KO:K06621]
p53 (mutation) [HSA:7157] [KO:K04451]
RB1 (mutation) [HSA:5925] [KO:K06618]
1,3-Butadiene [CPD:C16450]
Rubber industry
Busulfan [DR:D00248]
Thioguanine [DR:D06109]
Cytarabine [DR:D00168]
Imatinib mesylate [DR:D01441] (Philadelphia chromosome positive)
Dasatinib [DR:D06414] (Philadelphia chromosome positive)
Nilotinib hydrochloride hydrate [DR:D06413] (Philadelphia chromosome positive)
Bosutinib hydrate [DR:D09728] (Philadelphia chromosome positive)
Ponatinib hydrochloride [DR:D09951] (Philadelphia chromosome positive)
Hydroxyurea [DR:D00341]
Omacetaxine mepesuccinate [DR:D08956]
Sodium phosphate P 32 [DR:D05870]
ICD-O: 9875/3, Tumor type: Chronic myelogenous leukaemia
Other DBs
ICD-11: 2A20.0
ICD-10: C92.1
MeSH: D015464
PMID:15719031 (gene, tumor type)
Ren R.
Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia.
Nat Rev Cancer 5:172-83 (2005)
Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM.
The biology of chronic myeloid leukemia.
N Engl J Med 341:164-72 (1999)
Calabretta B, Perrotti D.
The biology of CML blast crisis.
Blood 103:4010-22 (2004)
PMID:16155477 (carcinogen)
Graff JJ, Sathiakumar N, Macaluso M, Maldonado G, Matthews R, Delzell E.
Chemical exposures in the synthetic rubber industry and lymphohematopoietic cancer mortality.
J Occup Environ Med 47:916-32 (2005)
PMID:9498905 (carcinogen)
Blair A, Kazerouni N.
Reactive chemicals and cancer.
Cancer Causes Control 8:473-90 (1997)
PMID:16873420 (carcinogen)
Alder N, Fenty J, Warren F, Sutton AJ, Rushton L, Jones DR, Abrams KR.
Meta-analysis of mortality and cancer incidence among workers in the synthetic rubber-producing industry.
Am J Epidemiol 164:405-20 (2006)
PMID:16299089 (carcinogen)
Sathiakumar N, Graff J, Macaluso M, Maldonado G, Matthews R, Delzell E.
An updated study of mortality among North American synthetic rubber industry workers.
Occup Environ Med 62:822-9 (2005)
PMID:15265366 (marker)
Chen ZX, Kaeda J, Saunders S, Goldman JM.
Expression patterns of WT-1 and Bcr-Abl measured by TaqMan quantitative real-time RT-PCR during follow-up of leukemia patients with the Ph chromosome.
Chin Med J (Engl) 117:968-71 (2004)
PMID:15661271 (marker)
Na IK, Kreuzer KA, Lupberger J, Dorken B, le Coutre P.
Quantitative RT-PCR of Wilms tumor gene transcripts (WT1) for the molecular monitoring of patients with accelerated phase bcr/abl + CML.
Leuk Res 29:343-5 (2005)
PMID:11529849 (marker)
Kreuzer KA, Saborowski A, Lupberger J, Appelt C, Na IK, le Coutre P, Schmidt CA.
Fluorescent 5'-exonuclease assay for the absolute quantification of Wilms' tumour gene (WT1) mRNA: implications for monitoring human leukaemias.
Br J Haematol 114:313-8 (2001)

» Japanese version

DBGET integrated database retrieval system