Valent P, Sperr W R, Samorapoompichit P, Geissler K, Lechner K, Horny H P, Bennett J M
Department of Internal Medicine I, Division of Hematology and Hemostaseology, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Leuk Res. 2001 Jul;25(7):595-602. doi: 10.1016/s0145-2126(01)00040-6.
Although mast cells (MC) appear to be myeloid cells, MC lineage involvement in myelogenous malignancies has been described only rarely. Based on clonal evolution, biology of afflicted cells, and disease criteria, three major groups of patients have been recognized: The first meets criteria for both diagnoses 'systemic mastocytosis' and 'associated hematologic clonal non-mast cell lineage disease (AHNMD)'. In such patients, myeloproliferative (MPS) or myelodysplastic syndromes (MDS), or acute myeloid leukemia (AML) is diagnosed apart from mastocytosis. In a second group of patients, large numbers of very immature MC-lineage cells (metachromatically granulated blast-like cells) are detectable, but the criteria to diagnose mastocytosis are not met. These patients have advanced myeloid neoplasms (MDS or MPS with blast cell increase, or AML) and variably suffer from mediator-related symptoms (flush, GI-tract ulcer, diarrhoea, coagulopathy). In some cases, the disease mimics mast cell- or basophilic leukemia. In contrast to basophilic leukemia, however, the metachromatic cells are strongly KIT+ and tryptase+. In contrast to true mast cell leukemia (MCL), MC do not form multifocal dense infiltrates in the bone marrow. Also, MC lack CD2 and CD25, and the C-KIT mutation Asp-816-Val. We propose the term 'myelomastocytic leukemia' or 'myelodysplastic mast cell syndrome' for these cases. In a third group of patients, myeloid neoplasms (MDS, MPS, AML) show constitutive expression of MC-associated antigens (tryptase, histamine) or mastocytosis-related gene defects (mutated C-KIT) without significant increase in metachromatic cells or criteria of mastocytosis. Whether these neoplasms display aberrant gene expression (or gene defects) or represent 'pre-pre-mast cell leukemias', remains unknown.
尽管肥大细胞（MC）似乎属于髓系细胞，但MC谱系参与髓系恶性肿瘤的情况却鲜有报道。基于克隆进化、受累细胞生物学特性及疾病标准，已识别出三大类患者：第一类符合“系统性肥大细胞增多症”和“相关血液学克隆性非肥大细胞谱系疾病（AHNMD）”这两种诊断标准。在此类患者中，除肥大细胞增多症外，还诊断出骨髓增殖性疾病（MPS）或骨髓增生异常综合征（MDS），或急性髓系白血病（AML）。在第二类患者中，可检测到大量极不成熟的MC谱系细胞（异染性颗粒状母细胞样细胞），但不符合肥大细胞增多症的诊断标准。这些患者患有晚期髓系肿瘤（伴有母细胞增多的MDS或MPS，或AML），并不同程度地出现与介质相关的症状（潮红、胃肠道溃疡、腹泻、凝血病）。在某些情况下，该疾病类似于肥大细胞或嗜碱性粒细胞白血病。然而，与嗜碱性粒细胞白血病不同的是，异染性细胞强烈表达KIT和类胰蛋白酶。与真性肥大细胞白血病（MCL）不同，MC在骨髓中不形成多灶性致密浸润。此外，MC缺乏CD2和CD25，且不存在C-KIT突变Asp-816-Val。我们建议将这些病例称为“髓肥大细胞白血病”或“骨髓增生异常肥大细胞综合征”。在第三类患者中，髓系肿瘤（MDS、MPS、AML）表现出MC相关抗原（类胰蛋白酶、组胺）的组成性表达或肥大细胞增多症相关基因缺陷（突变的C-KIT），而异染性细胞无明显增加，也不符合肥大细胞增多症的标准。这些肿瘤是否表现出异常基因表达（或基因缺陷），或者是否代表“前前肥大细胞白血病”，仍不清楚。
