Trka J, Zuna J, Haskovec C, Brabencová A, Kalinová M, Muzíková K, Paukertová R, Hrusák O, Zemanová Z, Michalová K, Starý J
II. dĕtská klinika 2. LF UK, Praha.
Cas Lek Cesk. 1999 Jan 4;138(1):12-7.
The BCR/ABL and MLL/AF4 fusion genes--resulting from t(9;22)(q34;q11) and t(4;11)(q21;q23) translocations, respectively--are considered as a high risk prognostic factors in children with acute lymphoblastic leukaemia (ALL). Their presence in malignant cells indicates patient for the most intensive antileukaemic therapy regardless of the other criteria. In contrast, the most common non-random chromosomal aberration in paediatric ALL--translocation t(12;21)(q12;q22)--is associated with a favourable prognosis. The examination of these rearrangements is important for the stratification of patients to the risk groups and also provides the most sensitive and specific tool for minimal residual disease (MRD) follow-up.
This study comprises 241 patients with ALL from Czech and Slovak Republics younger than 18 years at diagnosis. They were examined for presence of m-RNA of fusion genes BCR/ABL, MLL/AF4 and TEL/AML1 by reverse transcriptase-polymerase chain reaction (RT-PCR) method. Seven out of 197 (3.6%) carried MLL/AF4 fusion gene, but among infants it was 56% (5 out of 9). BCR/ABL positivity was found in 2.5% (7 out of 240) and TEL/AML1 in 21.7% (41 out of 189) cases. Event free survival (EFS) curves demonstrate the clinical impact of these hybrid genes on patients' prognosis. Moreover, we present the possibility of the monitoring of MRD levels in follow-up samples of these patients.
All particular rearrangements were found only in a cohort of patients with B-precursor ALL (or hybrid leukaemia), which constitutes 85% of our group. Presence of BCR/ABL or MLL/AF4 fusion gene is associated with poor prognosis and is indispensable condition for correct stratification of patients to the risk groups according to treatment protocols. Hybrid gene TEL/AML1 defines subgroup of children with better prognosis and due to its high frequency provides us with a very useful tool for MRD detection.
BCR/ABL和MLL/AF4融合基因分别由t(9;22)(q34;q11)和t(4;11)(q21;q23)易位产生，被认为是急性淋巴细胞白血病（ALL）患儿的高危预后因素。它们在恶性细胞中的存在表明患者无论其他标准如何都需要接受最强化的抗白血病治疗。相比之下，小儿ALL中最常见的非随机染色体畸变——t(12;21)(q12;q22)易位——与良好的预后相关。检测这些重排对于将患者分层到风险组很重要，并且还为微小残留病（MRD）随访提供了最敏感和特异的工具。
本研究包括241例来自捷克和斯洛伐克共和国的诊断时年龄小于18岁的ALL患者。通过逆转录聚合酶链反应（RT-PCR）方法检测他们是否存在融合基因BCR/ABL、MLL/AF4和TEL/AML1的mRNA。197例中有7例（3.6%）携带MLL/AF4融合基因，但在婴儿中这一比例为56%（9例中有5例）。BCR/ABL阳性在2.5%（240例中有7例）的病例中被发现，TEL/AML1在21.7%（189例中有41例）的病例中被发现。无事件生存期（EFS）曲线显示了这些融合基因对患者预后的临床影响。此外，我们展示了监测这些患者随访样本中MRD水平的可能性。
所有特定重排仅在B前体ALL（或混合白血病）患者队列中被发现，该队列占我们研究组的85%。BCR/ABL或MLL/AF4融合基因的存在与不良预后相关，并且是根据治疗方案将患者正确分层到风险组的必要条件。融合基因TEL/AML1定义了预后较好的儿童亚组，由于其高频率为我们提供了一个非常有用的MRD检测工具。
