急性髓性白血病混合谱系白血病基因重排的研究

Rearrangements of the mixed lineage leukemia gene in acute myeloid leukemia

目的对急性髓性白血病(AML)患者可能出现的混合谱系白血病(mixed lineage leukemia,MLL)基因重排进行研究,并探讨其临床意义。方法在常规细胞遗传学分析基础上运用分子生物学方法-荧光原位杂交技术(FISH),采用多种位点特异性DNA探针(染色体全染、特殊位点、双色或多色易位融合探针),对58例AML患者(47例成人AML,11例儿童AML)进行分析研究。结果有6例出现MLL基因重排,分别出现MLL基因的移位,复制及丢失,阳性率占10．3％。其中4例为成人AML,2例为儿童AML,除了MLL基因重排外,5例AML患者同时合并有复杂的核型变化,分别为:47-48,XX,der(1)t(1;17)(p36．1;q23),+4,+10,der(11)t(11;17)(q23;q23),-17,-18, +20,+21?.ish+21(wcp21+),der(1)t(1;17)(wcp17+),der(11)t(11;17)(wcp11+;wcp17 +);46,XX,del(5)(q13q33),r(11)(p15q25),+r(11)(p15q25)．ishr(11)(wcp11+,MLL+),+r (11)(wcp11+,MLL+);46,XY,del(11)(q23)[2]／46,idem,add(16)(p13．1)[8]／46,XY[10]．ishadd(16)(wcp16+),rea(11)(wcp11+);55,XY,+ markers．ish 11q23(MLL×3),+21(wcp21 +);46,XY,add(11)(q23)[6]／46,idem,t(15;17)(q22;q21)[12]／46,XY[2]．ish dup(11)(MLL ++),t(15;17)(PML+,RARa+;RARa-)[24]。结论急性髓性白血病常合并有MLL基因重排,本实验组的阳性率超过10％。由于MLL基因重排的患者具有对常规化疗不敏感及预后不良的特点,对初治急性白血病患者应常规进行MLL基因重排的检查。

Objective To study the frequency of mixed lineage leukemia （MLL） gene rearrangements in patients with acute myeloicl leukemia （AML） ancl to determine the significance thereof. Methods Conventional cytogenetics （CC） and karyotype analysis were conducted on the bone marrow ceils from 58 patients with acute myelocytic leukemia （AML）, 47 adults （aged 15 -67） and 11 children （aged 1 - 14）. Fluorescence in situ hybridization （FISH） using the whole chromosome painting （WCP） probes of the chromosomes 1,5, 11, 16, 17, and 21 was performed A total of 58 patients were included in this study. Forty - seven of these patients with AML were adults and the remaining were children. Both conventional cytogenetics （CC） and fluorescence in situ hybridization （FISH） were carried out. FISH analysis was performed utilizing commercially available DNA probes, including whole chromosome painting probes, locus specific probes, and specific and dual color/multiple color translocation fusion probes. Results Six out of the 58 patients （ 10.3% ） were found to have MLL gene rearrangements, either an extra signal of MLL gene or a disruption of MLL gene due to a translocation or deletion or duplication. Of these six patients with MLL gene rearrangements, four were adults and two were children. In addition to MLL gene rearrangements, complex chromosomal changes were also detected in five of these patients： 47-49,XX,der（1）t（1;17）（p6.1;q23）,＋4,＋10,der（11）t（11;17）（q23;q23）,-17,-18,＋20,＋21？.ish＋21（wcp21＋）,der（1）t（1;17）（wcp17＋）,der（11）t（11;17）（wcp11＋;wcp17＋）;46,XX,del（5）（q13q33）,r（11）（p15q25）,＋r（11）（p15q25）.ishr（11）（wcp11＋,MLL＋）,＋r（11）（wcp11＋,MLL＋）;46,XY,del（11）（q23）[2]/46,idem,add（16）（p13.1）[8]/46,XY[10].ishadd（16）（wcp16＋）,rea（11）（wcp11＋）;55,XY,＋markers.ish 11q23（MLL×3）,＋21（wcp21＋）;46,XY,add（11）（q23）[6]/46,idem,t（15;17）（q22;q21）[12]/46,XY[2].ish dup（11）（MLL＋＋）,t（15;17）（PML＋,RARa＋;RARa-）[24]. Conclusion MLL gene rearrangement is relatively common in AML patients. Because MLL gene arrangements due to translocation or other structural changes are associated with poor response to chemotherapy and poor prognosis, routine testing for this gene rearrangements should be provided to all newly diagnosed patients with AML.