Acute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation program. AML accounts for approximately 80% of all adult leukemias and remains the most common cause of leukemia death. Two major types of genetic events have been described that are crucial for leukemic transformation. A proposed necessary first event is disordered cell growth and upregulation of cell survival genes. The most common of these activating events were observed in the RTK Flt3, in N-Ras and K-Ras, in Kit, and sporadically in other RTKs. Alterations in myeloid transcription factors governing hematopoietic differentiation provide second necessary event for leukemogenesis. Transcription factor fusion proteins such as PML-RARalpha (in Acute promyelocytic leukemia, a subtype of AML), AML-ETO or PLZF-RARalpha block myeloid cell differentiation by repressing target genes. In other cases, the transcription factors themselves are mutated.
Category
Cancer
Brite
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Neoplasms of haematopoietic or lymphoid tissues
2A60 Acute myeloid leukaemias and related precursor neoplasms
H00003 Acute myeloid leukemia
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H00003 Acute myeloid leukemia
nt06530 PI3K signaling
H00003 Acute myeloid leukemia
Cellular process
nt06535 Efferocytosis
H00003 Acute myeloid leukemia
Tumor markers [br08442.html]
H00003
Cancer-associated carbohydrates [br08441.html]
H00003
Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H
Title
Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt.
Dong S, Zhu J, Reid A, Strutt P, Guidez F, Zhong HJ, Wang ZY, Licht J, Waxman S, Chomienne C, Chen Z, Zelent A, Chen SJ
Title
Amino-terminal protein-protein interaction motif (POZ-domain) is responsible for activities of the promyelocytic leukemia zinc finger-retinoic acid receptor-alpha fusion protein.
Illendula A, Pulikkan JA, Zong H, Grembecka J, Xue L, Sen S, Zhou Y, Boulton A, Kuntimaddi A, Gao Y, Rajewski RA, Guzman ML, Castilla LH, Bushweller JH
Title
Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFbeta-SMMHC delays leukemia in mice.
Zhang MY, Churpek JE, Keel SB, Walsh T, Lee MK, Loeb KR, Gulsuner S, Pritchard CC, Sanchez-Bonilla M, Delrow JJ, Basom RS, Forouhar M, Gyurkocza B, Schwartz BS, Neistadt B, Marquez R, Mariani CJ, Coats SA, Hofmann I, Lindsley RC, Williams DA, Abkowitz JL, Horwitz MS, King MC, Godley LA, Shimamura A
Title
Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.
Hahn CN, Chong CE, Carmichael CL, Wilkins EJ, Brautigan PJ, Li XC, Babic M, Lin M, Carmagnac A, Lee YK, Kok CH, Gagliardi L, Friend KL, Ekert PG, Butcher CM, Brown AL, Lewis ID, To LB, Timms AE, Storek J, Moore S, Altree M, Escher R, Bardy PG, Suthers GK, D'Andrea RJ, Horwitz MS, Scott HS
Title
Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia.
The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34.
So CW, Caldas C, Liu MM, Chen SJ, Huang QH, Gu LJ, Sham MH, Wiedemann LM, Chan LC
Title
EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human leukemia.
