Testoni N, Borsaru G, Martinelli G, Carboni C, Ruggeri D, Ottaviani E, Pelliconi S, Ricci P, Pastano R, Visani G, Zaccaria A, Tura S
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Italy.
Haematologica. 1999 Aug;84(8):690-4.
Acute myeloblastic leukemia (AML) with features of myelodysplastic syndrome (MDS) and abnormalities of megakaryocytopoiesis is often characterized by cytogenetic aberrations of the 3q21 and 3q26 bands involving inv(3)(q21q26) and (3;3)(q21;q26). These aberrations have been described in all FAB subtypes with the exception of M3, and in MDS and in megakaryoblastic crisis of chronic myeloid leukemia. We reviewed the biological and clinical features of 10 cases of AML with inv(3)(q21q26) and t(3;3)(q21;q26).
Four hundred and sixteen patients with AML were studied in our Institute by cytogenetic analysis and 10 (2.4%) showed inv(3)(q21q26) (7 patients) or t(3;3)(q21;q26) (3 patients): 7 males, 3 females; median age, 43.5 yrs. We also used RT-PCR to investigate the pattern of expression of the EVI-1 gene in 5 patients.
Additional chromosomal changes were demonstrated in 6 patients. In 5/10 cases a preceding MDS had been observed. A possible occupational exposure was established in 2 patients (a farmer and an histologist employing organic solvents) and another patient had a therapy-related leukemia. AML subtype was M1 in 9 patients and M2 in 1. A variable excess of micromegakaryocytes was observed in all the patients. In 5 patients the platelet count was normal or increased (median number: 172. 5x10(9)/L; range 55-440). Expression of EVI-1 gene was present in all the 5 patients studied. The clinical course and outcome was extremely poor: 9/10 patients were resistant and 1 patient showed a partial remission after induction therapy. Of the 9 patients resistant to the first line chemotherapy, 7 were also resistant to the second line chemotherapy. Three patients obtained a morphologic complete remission after third line chemotherapy (duration 1, 3 and 6 months); 2 of them were submitted to autologous bone marrow transplantation, but relapsed after 1 and 3 months. The median overall survival was 5.5 months.
Our findings evidence a strong correlation between 3q21q26 chromosomal aberrations, abnormalities of megakaryocytopoiesis and lack of response to conventional chemotherapy and support the diagnostic and prognostic relevance of chromosome characterization in the classification of AML.
具有骨髓增生异常综合征（MDS）特征及巨核细胞生成异常的急性髓系白血病（AML）常伴有3q21和3q26带的细胞遗传学畸变，包括inv(3)(q21q26)和(3;3)(q21;q26)。除M3外，所有FAB亚型、MDS以及慢性髓系白血病的巨核细胞危象中均有此类畸变的描述。我们回顾了10例伴有inv(3)(q21q26)和t(3;3)(q21;q26)的AML患者的生物学及临床特征。
我们研究所对416例AML患者进行了细胞遗传学分析，其中10例（2.4%）表现为inv(3)(q21q26)（7例）或t(3;3)(q21;q26)（3例）：男性7例，女性3例；中位年龄43.5岁。我们还采用逆转录聚合酶链反应（RT-PCR）研究了5例患者中EVI-1基因的表达模式。
6例患者存在其他染色体改变。10例中有5例之前观察到MDS。2例患者（1例农民和1例使用有机溶剂的组织病理学家）存在可能的职业暴露，另1例患者患有治疗相关白血病。AML亚型中9例为M1，1例为M2。所有患者均观察到不同程度的小巨核细胞增多。5例患者血小板计数正常或升高（中位数：172.5×10⁹/L；范围55 - 440）。所研究的5例患者中均存在EVI-1基因表达。临床病程及预后极差：10例患者中有9例耐药，1例诱导治疗后部分缓解。9例一线化疗耐药的患者中，7例对二线化疗也耐药。3例患者三线化疗后获得形态学完全缓解（持续时间分别为1、3和6个月）；其中2例接受了自体骨髓移植，但分别在1个月和3个月后复发。中位总生存期为5.5个月。
我们的研究结果表明3q21q26染色体畸变、巨核细胞生成异常与对传统化疗无反应之间存在密切关联，并支持染色体特征在AML分类中的诊断及预后相关性。
