Zhang Y, Poetsch M, Weber-Matthiesen K, Rohde K, Winkemann M, Haferlach T, Gassmann W, Ludwig W D, Grote W, Löffler H, Schlegelberger B
Department of Human Genetics, University of Kiel, Germany.
Br J Haematol. 1996 Mar;92(3):673-80. doi: 10.1046/j.1365-2141.1996.00399.x.
Three patients with secondary acute leukaemia after treatment with topoisomerase II inhibitor agents are described. Two patients had acute myeloid leukaemia (AML). FAB M5a, one had pro-B-acute lymphoblastic leukaemia (ALL). The interval between initiation of chemotherapy and the onset of secondary acute leukaemia was 19-20 months. 11q23 rearrangements were detected in all cases. They were due to translocations t(11;19) (q23;p13.3), t(11;16)(q23;p13) and t(4;11)(q21;q23), respectively. Fluorescence in situ hybridization (FISH) with Yeast Artificial Chromosome (YAC) probe 13HH4 spanning the ALL-1 gene on 11q23 confirmed that in each case the ALL-1 gene had been disrupted by the translocations. The study underlined the relationship between the development of secondary acute leukaemias with 11q23 rearrangement and previous chemotherapy with topisomerase II inhibitor agents. So far, however, only six adult patients with secondary ALL with t(4;11) after treatment with topoisomerase II inhibitor agents have been reported. All with t(4;11) mostly occurs in infants or young children. Our patient received epirubicin continuously for >19 months. This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL-1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors. Thus they may have a common biological background. This hypothesis was substantiated by means of combined immunophenotyping and FISH (FICTION). In the case of AML M5a with t(11;19), the tumour cells with ALL-1 rearrangement expressed CD34. Moreover, the pro-B-ALL with t(4;11) was CD34 positive. These findings suggest that the cell of origin of secondary AML and ALL with 11q23 rearrangement is an immature haemopoietic progenitor cell.
本文描述了3例在接受拓扑异构酶II抑制剂治疗后发生继发性急性白血病的患者。其中2例为急性髓系白血病（AML），FAB分型为M5a，1例为前B细胞急性淋巴细胞白血病（ALL）。化疗开始至继发性急性白血病发病的间隔时间为19 - 20个月。所有病例均检测到11q23重排，分别由t(11;19)(q23;p13.3)、t(11;16)(q23;p13)和t(4;11)(q21;q23)易位所致。用跨越11q23上ALL - 1基因的酵母人工染色体（YAC）探针13HH4进行荧光原位杂交（FISH）证实，在每例中ALL - 1基因均因易位而被破坏。该研究强调了伴有11q23重排的继发性急性白血病的发生与先前使用拓扑异构酶II抑制剂化疗之间的关系。然而，迄今为止，仅报道了6例在接受拓扑异构酶II抑制剂治疗后发生t(4;11)的成人继发性ALL患者。所有t(4;11)大多发生于婴幼儿。我们的患者连续接受表柔比星治疗>19个月。这表明累及ALL - 1基因的髓系和淋巴系白血病均可由外源性因素诱发，尤其是拓扑异构酶II抑制剂。因此它们可能具有共同的生物学背景。这一假说通过联合免疫表型分析和FISH（FICTION）得以证实。在伴有t(11;19)的AML M5a病例中，伴有ALL - 1重排的肿瘤细胞表达CD34。此外，伴有t(4;11)的前B - ALL也呈CD34阳性。这些发现提示，伴有11q23重排的继发性AML和ALL的起源细胞是未成熟的造血祖细胞。
