Miglino M, Varaldo R, Colombo N, Grasso R, Clavio M, Garuti A, Aquino S, Albarello A, Sessarego M, Gobbi M
Department of Hematology and Oncology, University of Genova, Genova, Italy.
J Exp Clin Cancer Res. 2006 Sep;25(3):321-4.
We carried out sequential molecular monitoring of different markers on two BCR-ABL positive ALL patients receiving a standard dose induction regimen, which was followed by a maintenance therapy that alternated imatinib and chemotherapy administration. Molecular study was performed at diagnosis, at the end of the induction phase, and then every three months during maintenance therapy. Each marrow sample underwent BCR-ABL analysis (p210 and p190 expression by RT-PCR and Real-time PCR) and monoclonal JH rearrangement analysis, while WT1 gene expression was detected by Real-time PCR. At diagnosis we detected high WT1 expression associated with the presence of both BCR-ABL transcripts and monoclonal JH rearrangement in both patients. Hematological remission, as well as a molecular status characterized by undetectable BCR-ABL expression, normal levels of WT1 expression, and persistence of monoclonal JH rearrangement, were achieved by both patients post-therapy. Follow up of patient 1 showed a progressive increase in WT-1 and in p-190 transcript, which was followed by cytogenetic and hematological relapse. We observed a progressive increase in the p210 transcript without a concomitant increase in WT-1 levels in patient 2. JH rearrangement was detected in all the samples analyzed. The molecular results may indicate the persistence of JH rearranged clonal cells with undetectable BCR-ABL. From a clinical point of view, our preliminary experience suggests that simultaneous analysis of BCR-ABL, JH and WT-1 expression may improve the study of MRD in Ph+ ALL.
我们对两名接受标准剂量诱导方案的BCR-ABL阳性急性淋巴细胞白血病（ALL）患者进行了不同标志物的序贯分子监测，随后进行了交替使用伊马替尼和化疗的维持治疗。在诊断时、诱导期结束时以及维持治疗期间每三个月进行一次分子研究。每份骨髓样本均进行BCR-ABL分析（通过逆转录聚合酶链反应（RT-PCR）和实时定量聚合酶链反应检测p210和p190表达）和单克隆JH重排分析，同时通过实时定量聚合酶链反应检测WT1基因表达。在诊断时，我们在两名患者中均检测到WT1高表达，且与BCR-ABL转录本和单克隆JH重排的存在相关。两名患者治疗后均实现了血液学缓解，以及以检测不到BCR-ABL表达、WT1表达水平正常和单克隆JH重排持续存在为特征的分子状态。对患者1的随访显示WT-1和p-190转录本逐渐增加，随后出现细胞遗传学和血液学复发。在患者2中，我们观察到p210转录本逐渐增加，而WT-1水平没有相应增加。在所有分析的样本中均检测到JH重排。分子结果可能表明存在JH重排的克隆细胞，其BCR-ABL检测不到。从临床角度来看，我们的初步经验表明，同时分析BCR-ABL、JH和WT-1表达可能会改善对Ph+ ALL微小残留病（MRD）的研究。
