Fonatsch C, Gudat H, Lengfelder E, Wandt H, Silling-Engelhardt G, Ludwig W D, Thiel E, Freund M, Bodenstein H, Schwieder G
Institut für Humangenetik, Medizinischen Universität zu Lübeck, Germany.
Leukemia. 1994 Aug;8(8):1318-26.
An inversion in the long arm of chromosome 3--inv(3)(q21q26)--or a translocation between both homologous chromosomes 3--t(3;3)(q21;q26)--is found specifically in myeloid neoplasias characterized by disturbances of thrombopoiesis and megakaryocyte development. Cytogenetic findings were correlated with clinical and hematological data in altogether 18 patients with acute nonlymphocytic leukemia (ANLL) and with inv(3) (13 patients) or t(3;3) (five patients), six of whom were male and 12 who were female. Chromosomal changes in addition to the 3q anomalies were demonstrated in 14 out of 18 patients, predominantly numerical and structural aberrations of chromosome 7 (12 cases) and/or abnormalities of 5q (five cases). Complex karyotype abnormalities were observed in six of 13 patients with inv(3), but in only one of five patients with t(3;3). In ten out of our 18 patients a preceding myelodysplastic syndrome (MDS) and/or exposure to mutagenic/carcinogenic agents had been established. In eight patients the morphology of ANLL blasts was immature (FAB subtype M1); in three patients ANLL-M4, and in two patients each ANLL-M5, M6, and M7 was diagnosed; in one patient with antecedent MDS the leukemic blasts were not classifiable according to the FAB criteria. A disturbed megakaryocyte development, characterized by an excess of micromegakaryocytes was observed in 14 patients, seven of them showed normal or elevated platelet counts as an unusual feature in patients with ANLL. The clinical course and outcome was extremely poor: 15 of 18 patients died within 10 months after the diagnosis of ANLL. Because of their missing response to conventional chemotherapy, patients with inv(3) or t(3;3) have to be estimated as at high risk. The characterization of genes affected by inv(3) or t(3;3) could help to elucidate molecular changes leading to impaired proliferation and differentiation of hematopoietic cells, also of the megakaryocytic lineage. Based on molecular genetic findings new therapeutical approaches could be designed.
3号染色体长臂倒位——inv(3)(q21q26)——或两条同源3号染色体之间的易位——t(3;3)(q21;q26)——特别见于以血小板生成和巨核细胞发育紊乱为特征的髓系肿瘤。对总共18例急性非淋巴细胞白血病（ANLL）患者的细胞遗传学结果与临床和血液学数据进行了关联分析，其中13例患者存在inv(3)，5例患者存在t(3;3)，其中6例为男性，12例为女性。18例患者中有14例除3q异常外还存在染色体改变，主要是7号染色体的数目和结构畸变（12例）和/或5q异常（5例）。13例inv(3)患者中有6例观察到复杂核型异常，但5例t(3;3)患者中只有1例观察到。18例患者中有10例曾有骨髓增生异常综合征（MDS）和/或接触诱变/致癌剂。8例患者的ANLL原始细胞形态不成熟（FAB亚型M1）；3例患者为ANLL-M4，2例患者分别诊断为ANLL-M5、M6和M7；1例既往有MDS的患者，其白血病原始细胞根据FAB标准无法分类。14例患者观察到巨核细胞发育紊乱，其特征为微小巨核细胞过多，其中7例患者血小板计数正常或升高，这在ANLL患者中是不寻常的特征。临床病程和预后极差：18例患者中有15例在诊断ANLL后10个月内死亡。由于对传统化疗无反应，inv(3)或t(3;3)患者被视为高危患者。对受inv(3)或t(3;3)影响的基因进行表征有助于阐明导致造血细胞（包括巨核细胞系）增殖和分化受损的分子变化。基于分子遗传学发现，可设计新的治疗方法。
