Bernasconi Paolo
Division of Haematology, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Br J Haematol. 2008 Sep;142(5):695-708. doi: 10.1111/j.1365-2141.2008.07245.x. Epub 2008 Jun 5.
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.
骨髓增生异常综合征（MDS）和急性髓系白血病（AML）均为造血干细胞疾病。然而，虽然通过克隆追踪实验已揭示白血病干细胞，但由于植入问题不佳，发育异常干细胞从未通过异种移植试验得到证实。这些植入困难可能归因于MDS基因损伤的独特性质，这些损伤确实能够重现疾病表型。年轻患者的MDS和AML具有克隆性但不同的染色体标记，而老年患者的MDS和AML则存在相似的缺陷。肿瘤抑制基因在MDS中的潜在作用已被推测但从未得到证实，而在AML中已确定I类和II类突变之间的协同作用。在MDS和AML中，基质细胞与肿瘤克隆之间的相互作用均被破坏。在早期MDS中，基质细胞和肿瘤细胞产生高水平的抑制性细胞因子，而在晚期MDS和AML中，它们产生高水平的抗凋亡分子。
