Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.
Blood Cells Mol Dis. 2013 Jan;50(1):33-8. doi: 10.1016/j.bcmd.2012.09.001. Epub 2012 Oct 3.
T-cell acute lymphoblastic leukemia is a heterogeneous malignancy originating from developing lymphocyte precursors likely due to mutations in genes regulating thymocyte differentiation. Here, we characterized mutation status of BCL11B and FLT3 genes, presumably involved in T-ALL, together with FBXW7 and NOTCH1 as known players in T-ALL in 65 pediatric T-cell acute lymphoblastic leukemia patients. We also aimed at the assessment of prognostic value of NOTCH1 and FBXW7 mutations in ALL-IC BFM 2002 protocol. FLT3 and BCL11B mutations were detected in 3% and 2% of patients, respectively. FBXW7 mutations were observed in 8% of patients, while NOTCH1 was mutated in 40%. No correlation was found between NOTCH1 and FBXW7 mutations and traditionally used clinical factors or molecular features. In total we have detected nine mutations, which have not been previously described by others. Eight of them were found in NOTCH1 and one in BCL11B gene. Observed frequencies of NOTCH1 and FBXW7 are in line with previous reports, thus confirming postulated participation of these two genes in T-ALL pathomechanism. Moreover, we report on mutation frequency of FLT3 and BCL11B, not extensively studied in T-ALL so far. Finally, we suggest a putative role of BLC11B as an oncogene in T-ALL pathogenesis.
T 细胞急性淋巴细胞白血病是一种起源于发育中淋巴细胞前体的异质性恶性肿瘤，可能由于调节胸腺细胞分化的基因发生突变所致。在这里，我们对 65 例儿科 T 细胞急性淋巴细胞白血病患者中可能参与 T-ALL 的 BCL11B 和 FLT3 基因以及已知的 T-ALL 中的 FBXW7 和 NOTCH1 的突变状态进行了特征描述。我们还旨在评估 ALL-IC BFM 2002 方案中 NOTCH1 和 FBXW7 突变的预后价值。FLT3 和 BCL11B 突变分别在 3%和 2%的患者中检测到。FBXW7 突变在 8%的患者中观察到，而 NOTCH1 突变在 40%的患者中观察到。NOTCH1 和 FBXW7 突变与传统使用的临床因素或分子特征之间未发现相关性。总共检测到 9 个以前未被其他人描述的突变。其中 8 个位于 NOTCH1 基因中，1 个位于 BCL11B 基因中。观察到的 NOTCH1 和 FBXW7 的频率与之前的报道一致，因此证实了这两个基因在 T-ALL 发病机制中的假定参与。此外，我们报告了 FLT3 和 BCL11B 的突变频率，这些在 T-ALL 中尚未广泛研究。最后，我们提出 BCL11B 作为 T-ALL 发病机制中的癌基因的假设作用。
