KEGG   DISEASE: Chronic myeloid leukemia (CML)Help
Entry
H00004                      Disease                                

Name
Chronic myeloid leukemia (CML)
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.
Category
Cancer
Brite
Human diseases [BR:br08402]
 Cancers
  Cancers of haematopoietic and lymphoid tissues
   H00004  Chronic myeloid leukemia (CML)
Human diseases in ICD-10 classification [BR:br08403]
 2. Neoplasms (C00-D48)
  C81-C96  Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
   C92  Myeloid leukaemia
    H00004  Chronic myeloid leukemia (CML)
Cancer-accociated carbohydrates [br08441.html]
 H00004
BRITE hierarchy
Pathway
Chronic myeloid leukemia
Gene
BCR-ABL (translocation) [HSA:613 25] [KO:K08878 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]
Carcinogen
1,3-Butadiene [CPD:C16450]
Rubber industry
Marker
BCR-ABL (translocation) [HSA:613 25]
WT1 [HSA:7490]
Drug
Imatinib mesylate (Gleevec) [DG:DG00710]
Nilotinib [DG:DG00716]
Dasatinib [DG:DG00714]
Comment
ICD-O: 9875/3, Tumor type: Chronic myelogenous leukaemia
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:15719031 (gene, tumor type)
  Authors
Ren R.
  Title
Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia.
  Journal
Nat Rev Cancer 5:172-83 (2005)
DOI:10.1038/nrc1567
Reference
PMID:10403855 (gene)
  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)
DOI:10.1056/NEJM199907153410306
Reference
PMID:14982876 (gene)
  Authors
Calabretta B, Perrotti D.
  Title
The biology of CML blast crisis.
  Journal
Blood 103:4010-22 (2004)
DOI:10.1182/blood-2003-12-4111
Reference
PMID:16155477 (carcinogen)
  Authors
Graff JJ, Sathiakumar N, Macaluso M, Maldonado G, Matthews R, Delzell E.
  Title
Chemical exposures in the synthetic rubber industry and lymphohematopoietic cancer mortality.
  Journal
J Occup Environ Med 47:916-32 (2005)
Reference
PMID:9498905 (carcinogen)
  Authors
Blair A, Kazerouni N.
  Title
Reactive chemicals and cancer.
  Journal
Cancer Causes Control 8:473-90 (1997)
Reference
PMID:16873420 (carcinogen)
  Authors
Alder N, Fenty J, Warren F, Sutton AJ, Rushton L, Jones DR, Abrams KR.
  Title
Meta-analysis of mortality and cancer incidence among workers in the synthetic rubber-producing industry.
  Journal
Am J Epidemiol 164:405-20 (2006)
DOI:10.1093/aje/kwj252
Reference
PMID:16299089 (carcinogen)
  Authors
Sathiakumar N, Graff J, Macaluso M, Maldonado G, Matthews R, Delzell E.
  Title
An updated study of mortality among North American synthetic rubber industry workers.
  Journal
Occup Environ Med 62:822-9 (2005)
DOI:10.1136/oem.2004.018176
Reference
PMID:15265366 (marker)
  Authors
Chen ZX, Kaeda J, Saunders S, Goldman JM.
  Title
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.
  Journal
Chin Med J (Engl) 117:968-71 (2004)
Reference
PMID:15661271 (marker)
  Authors
Na IK, Kreuzer KA, Lupberger J, Dorken B, le Coutre P.
  Title
Quantitative RT-PCR of Wilms tumor gene transcripts (WT1) for the molecular monitoring of patients with accelerated phase bcr/abl + CML.
  Journal
Leuk Res 29:343-5 (2005)
DOI:10.1016/j.leukres.2004.08.003
Reference
PMID:11529849 (marker)
  Authors
Kreuzer KA, Saborowski A, Lupberger J, Appelt C, Na IK, le Coutre P, Schmidt CA.
  Title
Fluorescent 5'-exonuclease assay for the absolute quantification of Wilms' tumour gene (WT1) mRNA: implications for monitoring human leukaemias.
  Journal
Br J Haematol 114:313-8 (2001)
DOI:10.1046/j.1365-2141.2001.02912.x
Reference
(drug)
  Authors
Papadakis MA and McPhee SJ |(ed)
  Title
Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition
  Journal
McGraw Hill Education

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