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Molecular pathways in myelodysplastic syndromes and acute myeloid leukemia: relationships and distinctions–a review
Author(s) -
Bernasconi Paolo
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07245.x
Subject(s) - myelodysplastic syndromes , stem cell , myeloid , haematopoiesis , biology , myeloid leukemia , cancer research , stromal cell , leukemia , immunology , phenotype , bone marrow , gene , genetics
Summary The myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are both hematopoietic stem cell disorders. However, while leukemic stem cells have been revealed by clonal tracking experiments, dysplastic stem cells have never been demonstrated by xeno‐transplantation assays because of poor engraftment problems. These engraftment difficulties may be due to the unique nature of MDS genetic lesions that are truly able to recapitulate the disease phenotype. MDS and AML of younger patients harbour clonal yet different chromosomal markers, whereas MDS and AML of the elderly present similar defects. Potential involvement of tumor suppressor genes in MDS has been hypothesized but never confirmed, while cooperation between class I and class II mutations has been identified in AML. The reciprocal interactions between stromal cells and neoplastic clones are disrupted in both MDS and AML. In early MDS, stromal and neoplastic cells produce high levels of inhibitory cytokines, whereas in advanced MDS and AML they produce high levels of anti‐apoptotic molecules.