Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences
Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences
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DOI：
10.1038/sj.leu.2404957
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发表时间：
2008-01-01
期刊：
影响因子：
11.4
通讯作者：
Pieters, R.
中科院分区：
文献类型：
--
作者：
van Grotel, M.;Meijerink, J. P. P.;Pieters, R.
儿童T细胞急性淋巴细胞白血病（T-ALL）的特征是染色体重排，可能在特定的发展阶段实施逮捕。我们研究了分子细胞遗传学异常和T细胞发育阶段之间的关系，以调查是否在特定阶段的停滞可以解释特定异常的预后意义。我们广泛研究了72例儿童T-ALL病例的遗传异常和转录因子表达、NOTCH 1突变和特异性CD标记物表达。HOX 11例为CD 1阳性，与皮质分期一致，但由于4/5例缺乏胞质β表达，发育停滞可能先于β选择。H 0X 11 L2特别限于未成熟和前AB发育阶段，但3/17例H 0X 11 L2成熟病例限于γ δ谱系。TAL 1重排仅限于α β谱系，大多数病例为TCR-α β阳性。NOTCH 1突变存在于所有分子细胞遗传学亚组中，不限于特定的发育阶段。CALM-AF 10与早期复发相关。TAL 1或HOX 11 L2重排分别与良好和不良结局趋势相关。高与低TAL 1表达水平的病例也显示出良好结局的趋势。TAL 1水平较低的病例大多数为HOX 11 L2或CALM-AF 10阳性。NOTCH 1突变不能预测结果。T细胞发育亚组的分类不能预测结局。
Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is characterized by chromosomal rearrangements possibly enforcing arrest at specific development stages. We studied the relationship between molecular- cytogenetic abnormalities and T-cell development stage to investigate whether arrest at specific stages can explain the prognostic significance of specific abnormalities. We extensively studied 72 pediatric T-ALL cases for genetic abnormalities and expression of transcription factors, NOTCH1 mutations and expression of specific CD markers. HOX11 cases were CD1 positive consistent with a cortical stage, but as 4/5 cases lacked cytoplasmatic-beta expression, developmental arrest may precede beta-selection. HOX11L2 was especially confined to immature and pre- AB developmental stages, but 3/17 HOX11L2 mature cases were restricted to the gamma delta-lineage. TAL1 rearrangements were restricted to the alpha beta-lineage with most cases being TCR-alpha beta positive. NOTCH1 mutations were present in all molecular-cytogenetic subgroups without restriction to a specific developmental stage. CALM-AF10 was associated with early relapse. TAL1 or HOX11L2 rearrangements were associated with trends to good and poor outcomes, respectively. Also cases with high vs low TAL1 expression levels demonstrated a trend toward good outcome. Most cases with lower TAL1 levels were HOX11L2 or CALM-AF10 positive. NOTCH1 mutations did not predict for outcome. Classification into T-cell developmental subgroups was not predictive for outcome.