目的:这项研究旨在确定新诊断的急性淋巴细胞白血病(ALL)年龄<19岁的儿童染色体畸变的频率,在儿科和放射科就诊/入院,政府医学院,查谟.此外,我们旨在研究细胞遗传学分子异常与即时临床结局(诱导缓解)之间的相关性.
方法:这是一项前瞻性研究,为期2年(2011年5月至2013年5月),在印度一家三级保健医院进行。40名儿科(1-19岁)患者(18名男性,22名女性;M:F=0.8:1)对新诊断的ALL进行了分子细胞遗传学分析。从患者的父母获得书面同意。进行骨髓穿刺以诊断ALL。失去随访和未能同意的儿童被排除在调查之外。从患者获得宿主因子和临床参数。
结果:对40例确诊的ALL患者的骨髓抽取物样本进行常规细胞遗传学分析,采用逆转录-聚合酶链反应(RT-PCR)技术进行分子分析。在18/40(45%)的病例中获得了分布良好的中期板用于分析。RT-PCR显示20/40(50%)患者的基因异常。分子细胞遗传学分析的结果与患者的临床和血液学参数相关,以进行风险分层和立即结果(诱导缓解)。40例中有18例(45%)未发现异常。在其余22个案件中,8有TEL-AML1(20%),6人患有BCR-ABL(15%),4有MLL-AF4(10%),2具有E2A-PBX1(5%)融合基因,和2有超二倍体。最后,在这项研究中,较高比例的病例表现出不良易位,如t(9;22),t(4;11),和t(1;19)与文献报道的相比。
结论:RT-PCR检测可用于检测具有预后意义的癌基因融合转录本。在我们对40名患者的研究中,我们发现模式和频率与西方文献报道的不同。我们的研究表明,在儿童ALL中,超二倍体的频率较低(5%),而BCR-ABL基因融合的频率较高(20%)。最重要的是,与以前关于儿童ALL的研究相反,我们的研究表明女性占主导地位,男女比例为0.8:1。除了BCR-ABL融合基因,没有其他人与不良预后相关。已经确定的是,在诊断时对遗传实体的表征对于ALL的理解和最佳治疗是至关重要的。因为我们人口的畸变与西方人口的畸变有很大不同,我们可能需要调整我们的协议。
OBJECTIVE: This
study was conducted to determine the frequency of chromosomal aberrations in children aged <19 years with newly diagnosed acute lymphoblastic leukemia (ALL), attending/admitted in the Department of Pediatrics and Radiotherapy, Government Medical College, Jammu. Furthermore, we aimed to
study the correlation between the cytogenetic molecular abnormalities and the immediate clinical outcome (induction of remission).
METHODS: This was a prospective
study conducted over a period of 2 years (May 2011 to May 2013) in a tertiary care hospital in India. Forty pediatric (1-19 years) patients (18 males, 22 females; M: F = 0.8 : 1) with newly diagnosed ALL were studied for molecular cytogenetic analysis. Written consent was obtained from the parents of the patients. Bone marrow aspiration was done for making the diagnosis of ALL. Children lost to follow-up and who failed to give consent were excluded from the survey. Host factors and clinical parameters were obtained from patients.
RESULTS: Bone marrow aspirate samples of 40 diagnosed cases of ALL were subjected to routine cytogenetic analysis, and reverse transcription-polymerase chain reaction (RT-PCR) technique was used for molecular analysis. Well-spread metaphase plates were obtained in 18/40 (45%) cases for analysis. RT-PCR revealed abnormal genes in 20/40 (50%) patients. The results of molecular cytogenetic analysis were correlated with patients\' clinical and hematological parameters for risk stratification and immediate outcome (induction of remission). Eighteen out of 40 (45%) cases revealed no abnormality. Among the remaining 22 cases, 8 had TEL-AML1 (20%), 6 had BCR-ABL (15%), 4 had MLL-AF4 (10%), 2 had E2A-PBX1 (5%) fusion genes, and 2 had hyperdiploidy. To conclude, a higher proportion of cases in this
study showed adverse translocations such as t (9;22), t (4;11), and t (1;19) compared to that reported in literature.
CONCLUSIONS: RT-PCR assay was useful in detecting the prognostically significant oncogene fusion transcripts. In our study of 40 patients, we found that the pattern and frequency differ from those reported in Western literature. Our
study reveals a lower frequency of hyperdiploidy (5%) and a higher frequency of BCR-ABL gene fusion (20%) in childhood ALL. Above all, in contrast to previous studies on childhood ALL, our study showed female predominance, with the male-to-female ratio being 0.8 : 1. Apart from the BCR-ABL fusion gene, none other was associated with poor prognosis. It is already well established that the characterization of the genetic entities at diagnosis is crucial for the understanding and the optimal treatment of ALL. Because the aberrations in our population differ significantly from those reported in Western populations, we may be required to tailor our protocols.