Fagioli F, Cuneo A, Piva N, Carli M G, Previati R, Balboni M, Tomasi P, Cariani D, Scapoli G, Castoldi G
Institute of Hematology, University of Ferrara, Italy.
Cancer. 1992 Jul 1;70(1):77-85. doi: 10.1002/1097-0142(19920701)70:1<77::aid-cncr2820700113>3.0.co;2-c.
To study the correlation of environmental exposure to potentially mutagenic agents and the clinicopathologic picture in acute myeloid leukemia (AML), clinical features, morphologic characteristics, immunophenotype, and cytogenetics were studied in 59 patients with newly diagnosed AML.
Based on interviews on occupational hazards and hobbies showing prolonged contact with pesticides (18 patients) and organic solvents (7 patients), 25 patients were categorized as "exposed". Thirty-four patients were categorized as "unexposed,", based on anamnestic findings.
Light microscopic studies showed myelodysplasia involving multiple cell lineages in all assessable patients with professional exposure to pesticides and organic solvents, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in unexposed patients. These findings were confirmed by electron microscopic studies in 31 patients. Immunologic analysis showed the presence of a minor megakaryoblastic component in six exposed patients and showed positive findings for the CD34 stem cell marker in 85% of exposed patients, a figure significantly higher as compared with that for unexposed subjects. Cytogenetic studies confirmed the frequent occurrence of 5q and/or 7q aberrations in patients occupationally exposed (10 of 25 cases). Other recurring chromosome aberrations in the exposed group were 17p-, trisomy 11q, and translocation of 16q, 6p, 7p, and 11p, whereas the classic AML-specific translocations (i.e., t[15;17]; t[8;21]) were detected only in unexposed subjects. Conventional chemotherapy achieved complete remission in 1 of 19 exposed patients, as opposed to 14 of 29 unexposed patients, with a median survival of 2 months in the former group and 8 months in the latter.
Taken together, these findings document that AML in patients professionally exposed to toxic substances may represent a distinct cytogenetic and clinicopathologic entity. The clinicobiologic characteristics in these exposed patients are similar to the features of AML arising in patients with prior chemotherapy for another tumor, thus suggesting that similar transformation pathways may underlie leukemogenesis induced by cytotoxic drugs and by environmental exposure to some pesticides or organic solvents.
为研究急性髓系白血病(AML)患者环境暴露于潜在诱变剂与临床病理表现之间的相关性,对59例新诊断的AML患者的临床特征、形态学特征、免疫表型及细胞遗传学进行了研究。
根据职业危害和爱好访谈显示长期接触农药(18例患者)和有机溶剂(7例患者),将25例患者归类为“暴露组”。根据既往史,将34例患者归类为“非暴露组”。
光学显微镜研究显示,所有可评估的职业性接触农药和有机溶剂的患者均存在涉及多个细胞系的骨髓发育异常,而非暴露组患者非原始细胞群体的形态学异常仅局限于少数细胞。31例患者的电子显微镜研究证实了这些发现。免疫分析显示,6例暴露组患者存在少量巨核母细胞成分,85%的暴露组患者CD34干细胞标志物呈阳性,这一比例显著高于非暴露组患者。细胞遗传学研究证实,职业暴露患者(25例中的10例)频繁出现5号染色体长臂和/或7号染色体长臂异常。暴露组其他反复出现的染色体异常包括17号染色体短臂缺失、11号染色体三体以及16号染色体长臂、6号染色体短臂、7号染色体短臂和11号染色体短臂易位,而经典的AML特异性易位(即t[15;17];t[8;21])仅在非暴露组患者中检测到。传统化疗使19例暴露组患者中的1例达到完全缓解,而29例非暴露组患者中有14例达到完全缓解,前一组的中位生存期为2个月,后一组为8个月。
综上所述,这些发现表明职业性接触有毒物质的患者发生的AML可能代表一种独特的细胞遗传学和临床病理实体。这些暴露组患者的临床生物学特征与先前因另一种肿瘤接受化疗的患者发生的AML特征相似,因此提示细胞毒性药物以及环境暴露于某些农药或有机溶剂诱导白血病发生的过程可能存在相似的转化途径。