Safavi Setareh, Hansson Markus, Karlsson Karin, Biloglav Andrea, Johansson Bertil, Paulsson Kajsa
Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
Division of Hematology, Skåne University Hospital, Lund University;
Haematologica. 2015 Jan;100(1):55-61. doi: 10.3324/haematol.2014.112912. Epub 2014 Sep 26.
In contrast to acute lymphoblastic leukemia in children, adult cases of this disease are associated with a very poor prognosis. In order to ascertain whether the frequencies and patterns of submicroscopic changes, identifiable with single nucleotide polymorphism array analysis, differ between childhood and adult acute lymphoblastic leukemia, we performed single nucleotide polymorphism array analyses of 126 adult cases, the largest series to date, including 18 paired diagnostic and relapse samples. Apart from identifying characteristic microdeletions of the CDKN2A, EBF1, ETV6, IKZF1, PAX5 and RB1 genes, the present study uncovered novel, focal deletions of the BCAT1, BTLA, NR3C1, PIK3AP1 and SERP2 genes in 2-6% of the adult cases. IKZF1 deletions were associated with B-cell precursor acute lymphoblastic leukemia (P=0.036), BCR-ABL1-positive acute lymphoblastic leukemia (P<0.001), and higher white blood cell counts (P=0.005). In addition, recurrent deletions of RASSF3 and TOX were seen in relapse samples. Comparing paired diagnostic/relapse samples revealed identical changes at diagnosis and relapse in 27%, clonal evolution in 22%, and relapses evolving from ancestral clones in 50%, akin to what has previously been reported in pediatric acute lymphoblastic leukemia and indicating that the mechanisms of relapse may be similar in adult and childhood cases. These findings provide novel insights into the leukemogenesis of adult acute lymphoblastic leukemia, showing similarities to childhood disease in the pattern of deletions and the clonal relationship between diagnostic and relapse samples, but with the adult cases harboring additional aberrations that have not been described in pediatric acute lymphoblastic leukemia.
与儿童急性淋巴细胞白血病不同，成人急性淋巴细胞白血病的预后很差。为了确定通过单核苷酸多态性阵列分析可识别的亚微观变化的频率和模式在儿童和成人急性淋巴细胞白血病之间是否存在差异，我们对126例成人病例进行了单核苷酸多态性阵列分析，这是迄今为止最大的系列病例，其中包括18对诊断和复发样本。除了识别CDKN2A、EBF1、ETV6、IKZF1、PAX5和RB1基因的特征性微缺失外，本研究还在2%至6%的成人病例中发现了BCAT1、BTLA、NR3C1、PIK3AP1和SERP2基因的新的局灶性缺失。IKZF1缺失与B细胞前体急性淋巴细胞白血病相关（P = 0.036）、BCR-ABL1阳性急性淋巴细胞白血病相关（P < 0.001）以及白细胞计数较高相关（P = 0.005）。此外，在复发样本中还发现了RASSF3和TOX的复发性缺失。比较配对的诊断/复发样本发现，27%的样本在诊断和复发时变化相同，22%的样本发生克隆进化，50%的复发样本由祖先克隆演变而来，这与之前在儿童急性淋巴细胞白血病中的报道相似，表明成人和儿童病例的复发机制可能相似。这些发现为成人急性淋巴细胞白血病的白血病发生提供了新的见解，显示出在缺失模式以及诊断和复发样本之间的克隆关系方面与儿童疾病相似，但成人病例存在儿童急性淋巴细胞白血病中未描述的其他畸变。
