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 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
Pathway-based classification of diseases [BR:br08402]
 Signal transduction
  nt06526  MAPK signaling
   H00004  Chronic myeloid leukemia
Cancer-associated carbohydrates [br08441.html]
hsa05220  Chronic myeloid leukemia
nt06276 Chronic myeloid leukemia
BCR-ABL (translocation) [HSA:613 25] [KO:K08878 K06619]
MECOM (overexpression) [HSA:2122] [KO:K04462]
RUNX1 (translocation) [HSA:861] [KO:K08367]
CDKN2A [HSA:1029] [KO:K06621]
TP53 [HSA:7157] [KO:K04451]
RB1 [HSA:5925] [KO:K06618]
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] (T315I positive)
Asciminib hydrochloride [DR:D11404] (mutation positive)
Hydroxyurea [DR:D00341]
Omacetaxine mepesuccinate [DR:D08956]
Sodium phosphate P 32 [DR:D05870]
Other DBs
ICD-11: 2A20.0
ICD-10: C92.1
MeSH: D015464
OMIM: 608232
PMID:15719031 (BCR-ABL, MECOM, RUNX1, CDKN2A, TP53, RB1)
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)

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