混合系白血病基因相关白血病骨髓细胞形态学特征

The morphological characters of MLL related leukemia

目的通过观察混合系白血病(Mixed lineage leukemia, MLL)基因相关白血病患者骨髓细胞形态学特征,了解MLL基因重排特征与FAB形态学分型的关系.方法用多重巢式RT-PCR方法检测214例白血病和淋巴瘤的常见白血病相关融合基因,选择有MLL基因异常的白血病患者骨髓细胞涂片做光镜下的形态学观察,比较具有不同MLL基因异常的白血病细胞的形态学差异.结果患者中发现MLL基因异常者14例,其中有 MLL/AF6融合基因者5例,骨髓细胞形态学均为FAB-M5型,具有典型的原始单核细胞白血病的特征:在光镜下均表现为细胞体积大,染色质疏松,细胞核折叠,有1～2个大而清晰的核仁,胞质嗜碱性呈毛玻璃样.多数细胞核旁淡染区明显,胞浆内可见细长型奥氏小体,染色体纤细.过氧化物酶染色阴性,非特异脂酶染色阳性,可被氟化钠抑制.其他MLL基因异常7例,包括MLL部分串联重复(PTD),MLL/AF10融合基因,MLL/AF4阳性者,分别属于M1,M4型,MDS和幼稚淋细胞白血病.结论 MLL基因异常主要见于与单核细胞相关的白血病,MLL/AF6重排可能是急性原始单核细胞型白血病一种独立亚型的重要标志,该融合基因可能与单核细胞分化有更密切的关系.

Objective To characterize the morphological feature of mixed lineage leukemia (MLL) gene related leukemia, and determine the correlation of MLL rearrangements with FAB subtypes. MethodsWe screened 214 of leukemia samples with multiplex RT-PCR to detect positive samples with MLL rearrangement, then described the morphological characters and compared with FAB classification criteria.Results Among the leukemia and lymphomas, we identified 14 samples harboring various MLL rearrangements, including 5 of MLL/AF6, 7 of MLL partial tandem duplication (PTD) and 1 of MLL/AF10. We also detected 1 of MLL/AF4 among 11 MDS,All of AML with MLL/AF6 fusion gene were M5 with classic monoblastic characters: large blast cells with delicate, lacy chromatin, presenting one to two large prominent nucleoli. The cytoplasm was voluminous, basophilic and grayish groundglass appearance with fine azurophilic granules. A few cells contained fine and long Auer rods. Cytochemically, these cells were negative for peroxidase, some cells demonstrated weak scattered peroxidase activity. The reactivity of these cells for nonspecific esterase was inhibited by sodium fluoride. The morphology of leukemia with MLL PTD is more divergent, as 1 of M1, 3 of M4 and 1 of M5 and 1 of prelymphoblastic leukemia.Conclusion MLL rearrangements mostly occurred in leukemia related to monoblastic lineage, including M4 and M5. All of MLL/AF6 fusion leukemia belong to M5, implying this type of fusion gene might be involved in monocytic differentiation and maturation.