期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms23115950
关键词
ELN classification; AML; FLT3-ITD with wild-type NPM1; DEK-NUP214 fusion; KMT2A rearrangement; BCR-ABL1 fusion; haploinsufficiency of GATA2 and mis-expression of MECOM; RUNX1 mutation; ASXL1 mutation; TP53 mutation; complex karyotype; menin; anti-CD47 antibody
资金
- National Cancer Research and Development expenses grant [2021-A-11]
- National Cancer Center, Japan
The European LeukemiaNet (ELN) criteria define the adverse genetic factors of acute myeloid leukemia (AML), which are associated with resistance to standard chemotherapy and poor prognosis. Different adverse genetic factors often rely on common pathways and can be found in at least one in eight AML patients. TP53 mutation is particularly associated with poor prognosis.
The European LeukemiaNet (ELN) criteria define the adverse genetic factors of acute myeloid leukemia (AML). AML with adverse genetic factors uniformly shows resistance to standard chemotherapy and is associated with poor prognosis. Here, we focus on the biological background and real-world etiology of these adverse genetic factors and then describe a strategy to overcome the clinical disadvantages in terms of targeting pivotal molecular mechanisms. Different adverse genetic factors often rely on common pathways. KMT2A rearrangement, DEK-NUP214 fusion, and NPM1 mutation are associated with the upregulation of HOX genes. The dominant tyrosine kinase activity of the mutant FLT3 or BCR-ABL1 fusion proteins is transduced by the AKT-mTOR, MAPK-ERK, and STAT5 pathways. Concurrent mutations of ASXL1 and RUNX1 are associated with activated AKT. Both TP53 mutation and mis-expressed MECOM are related to impaired apoptosis. Clinical data suggest that adverse genetic factors can be found in at least one in eight AML patients and appear to accumulate in relapsed/refractory cases. TP53 mutation is associated with particularly poor prognosis. Molecular-targeted therapies focusing on specific genomic abnormalities, such as FLT3, KMT2A, and TP53, have been developed and have demonstrated promising results.
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