Kjeldsen Eigil, Roug Anne Stidsholt
Cancer Cytogenetics Laboratory, Department of Hematology, Aarhus University Hospital, Tage-Hansensgade 2, DK-8000, Aarhus C, Denmark.
Mol Cytogenet. 2012 May 1;5(1):21. doi: 10.1186/1755-8166-5-21.
We here describe a novel unbalanced de novo translocation der(5)t(4;5)(q26;q21.1) in a 39-year-old male diagnosed with acute T-cell lymphoblastic leukemia. Bone marrow (BM) was massively infiltrated with 85 % highly proliferative polymorphic T-cell precursors. Immunologically, the malignant cells stained positive for CD7, CD34, intracytoplasmic CD3+, TdT + and negative for CD3 and CD5. G-banded chromosome analysis of BM cells showed the normal karyotype 46,XY[25] whereas BAC-based aCGH analysis revealed partial gain of 4q and partial loss of 5q. Multicolor karyotyping confirmed the presence of an unbalanced der(5)t(4;5) as the sole structural abnormality. Subsequent high-resolution oligonucleotide-based aCGH analysis showed that the der(5)t(4;5)(q26;q21.1) resulted in partial trisomy of 4q26qter (117,719,015-190,613,014) and partial monosomy of 5q21.1qter (100,425,442-180,857,866) and that there was no indication of any gene disruptions resulting from the breakages. Interphase FISH analysis using BAC-based specific probes for 4q26 and 5q21.1 confirmed the breakpoints and revealed approximately 80 % abnormal cells accordingly. At 4q26 the MIR1973 gene is located centromeric to the breakpoint in the copy number neutral region and the TRAM1L1 gene is located within the gained region. At 5q21.1 the genes ST8SIA4 and MIR548p are located centromeric to the breakpoint and no known genes up to approximately 1 Mb telomeric to the breakpoint in the copy number loss region. Interestingly, only the gene ST8SIA4 at 5q21.1 have been implicated in T-cell regulation as it encodes one of the key enzymes for polysialysation of surface proteins on dendritic cells which are important regulators for T-cell proliferation. The der(5)t(4;5) is thought to play a crucial role in the pathogenesis of acute T-ALL due to either gain of 4q, the loss of 5q, or deregulation of genes in proximity to the breakpoints.
我们在此描述了一名39岁被诊断为急性T细胞淋巴细胞白血病的男性患者中一种新的不平衡的从头易位der(5)t(4;5)(q26;q21.1)。骨髓（BM）被85%高度增殖的多形性T细胞前体大量浸润。免疫方面，恶性细胞CD7、CD34、胞浆内CD3+、TdT+染色呈阳性，而CD3和CD5染色呈阴性。对BM细胞进行G带染色体分析显示核型正常为46,XY[25]，而基于BAC的aCGH分析显示4q部分增加和5q部分缺失。多色核型分析证实存在不平衡的der(5)t(4;5)作为唯一的结构异常。随后基于高分辨率寡核苷酸的aCGH分析表明，der(5)t(4;5)(q26;q21.1)导致4q26qter（117,719,015 - 190,613,014）部分三体和5q21.1qter（100,425,442 - 180,857,866）部分单体，且没有迹象表明断裂导致任何基因破坏。使用基于BAC的针对4q26和5q21.1的特异性探针进行间期FISH分析证实了断点，并相应地显示约80%的异常细胞。在4q26，MIR1973基因位于拷贝数中性区域断点的着丝粒侧，TRAM1L1基因位于获得区域内。在5q21.1，ST8SIA4和MIR548p基因位于断点的着丝粒侧，在拷贝数缺失区域断点端粒侧约1 Mb范围内没有已知基因。有趣的是，只有5q21.1处的ST8SIA4基因与T细胞调节有关，因为它编码树突状细胞表面蛋白多唾液酸化的关键酶之一，而树突状细胞是T细胞增殖的重要调节因子。由于4q的增加、5q的缺失或断点附近基因的失调，der(5)t(4;5)被认为在急性T淋巴细胞白血病的发病机制中起关键作用。
