Department of Paediatrics, Government Medical College, Jammu, Jammu and Kashmir, India.
Clin Med Insights Oncol. 2015 Mar 24;9:39-42. doi: 10.4137/CMO.S24463. eCollection 2015.
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).
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.
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.
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.
本研究旨在确定在加马刀放射治疗中心儿科就诊/住院的年龄<19 岁的新发急性淋巴细胞白血病（ALL）患儿的染色体畸变频率。此外，我们旨在研究细胞遗传学分子异常与即刻临床结果（诱导缓解）之间的相关性。
这是一项在印度的一家三级保健医院进行的为期 2 年的前瞻性研究（2011 年 5 月至 2013 年 5 月）。对 40 名新诊断为 ALL 的儿科患者（男 18 例，女 22 例；M：F=0.8：1）进行了分子细胞遗传学分析。从患者的父母那里获得了书面同意。骨髓抽吸术用于诊断 ALL。未随访和未同意的患儿被排除在调查之外。从患儿处获得宿主因素和临床参数。
对 40 例 ALL 确诊病例的骨髓抽吸样本进行常规细胞遗传学分析，并采用逆转录-聚合酶链反应（RT-PCR）技术进行分子分析。18/40（45%）例获得良好分散的中期染色体。20/40（50%）例患者的 RT-PCR 显示异常基因。对分子细胞遗传学分析结果与患者的临床和血液学参数进行了风险分层和即刻结果（诱导缓解）的相关性分析。40 例中有 18 例（45%）未发现异常。在其余 22 例中，8 例有 TEL-AML1（20%），6 例有 BCR-ABL（15%），4 例有 MLL-AF4（10%），2 例有 E2A-PBX1（5%）融合基因，2 例有超二倍体。总之，与文献报道相比，本研究中更多的病例显示出不良易位，如 t（9；22）、t（4；11）和 t（1；19）。
RT-PCR 检测在检测预后有意义的癌基因融合转录本方面是有用的。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。我们的研究显示，儿童 ALL 中的超二倍体（5%）频率较低，BCR-ABL 基因融合（20%）频率较高。最重要的是，与以往对儿童 ALL 的研究相比，我们的研究显示女性占优势，男女比例为 0.8：1。除了 BCR-ABL 融合基因外，其他任何基因都与预后不良无关。已经确定的是，在诊断时对遗传实体的特征描述对于理解和优化 ALL 的治疗至关重要。由于我们人群中的异常与西方人群中的异常有显著差异，我们可能需要调整我们的方案。
