Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

Background: Chromosomal aberrations identified in acute lymphoblastic leukemia (ALL) have an important role in disease diagnosis, prognosis and management. Information on karyotype and associated clinical parameters are essential to physicians for planning cancer control interventions in different geographical regions. Materials and Methods: In this study, we present the overall frequency and distribution patterns of chromosomal aberrations in both children and adult de novo B lineage ALL Indian patients using conventional cytogenetics, interphase FISH and multiplex RT-PCR. Results: Among the 215 subjects, cytogenetic results were achieved in 172 (80%) patients; normal karyotype represented 37.2% and abnormal 62.8% with a distribution as follows: 15.3% hypodiploidy; 10.3% hyperdiploidy; 15.8% t(9;22); 9.8% t(1;19); 3.7% t(12;21); 2.8% t(4;11); 2.8% complex karyotypes. Apart from these, we observed several novel, rare and common chromosomal rearrangements. Also, FISH studies using LSI extra-signal dual-color probes revealed additional structural or numerical changes. Conclusions: These results demonstrate cytogenetic heterogeneity of ALL and confirm that the incidence of chromosomal abnormalities varies considerably. To the best of our knowledge, this is one of the largest reported series of cytogenetic investigations in Indian B-lineage ALL cases. In addition, ongoing cytogenetic studies are warranted in larger groups of B-lineage ALL cases to identify newly acquired chromosomal abnormalities that may contribute to disease diagnosis and management.

Section: Distributions Of Chromosomal Rearrangementsmentioning

confidence: 88%

Cytogenetic Profile of De Novo B lineage Acute Lymphoblastic Leukemia: Determination of Frequency, Distribution Pattern and Identification of Rare and Novel Chromosomal Aberrations in Indian Patients

Bhandari¹,

Ahmad²,

Dalvi³

et al. 2015

“…The incidence of ALL appears to be highest in Hispanic children (43 cases per 1 million), and the incidence is substantially higher in white children than in black children, with a nearly three times higher incidence from age 2 to 3 in white children than in black children (Smith et al, 1999;National Cancer Institute, 2012 a;b). Awan et al (2012) reported that the frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Their data indicated that an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.…”

Section: Introductionmentioning

confidence: 99%

New Haplotypes of the ATP Synthase Subunit 6 Gene of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia in Saudi Arabia

Yacoub¹,

Mahmoud²,

El-Baz³

et al. 2015

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Aim and Objectives: This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. Results: The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. Conclusions: These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

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Asian Pac J Cancer Prev, 15 (22), 9961-9966

IntroductionThe Philadelphia chromosome (Ph), t (9; 22) (q34; q11.2) is transcribed into a fusion gene, BCR-ABL (Awan et al, 2012;Sabir et al, 2012). This translocation is one of the most common genetic abnormalities detected in leukemia.

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mentioning

confidence: 99%

Clinical Significance of BCR-ABL Fusion Gene Subtypes in Chronic Myelogenous and Acute Lymphoblastic Leukemias

Zhou²,

Zhou³

et al. 2014

Asian Pac J Cancer Prev, 15 (22), 9961-9966 IntroductionThe Philadelphia chromosome (Ph), t (9; 22) (q34; q11.2) is transcribed into a fusion gene, BCR-ABL (Awan et al., 2012;Sabir et al., 2012). This translocation is one of the most common genetic abnormalities detected in leukemia. The site of the breakpoint in the BCR gene may influence the phenotype of diseases. In the vast majority of patients, the breakpoints in the BCR gene are clustered within three well-defined regions: (I) a 55 kb sequence of the first intron, called the minor breakpoint cluster region (m-bcr); (II) a 5.8 kb region spanning exons 12-16, called the major breakpoint cluster region (M-bcr), and finally; (III) intron 19, called μ-bcr. The resultant fusion transcript (e1-a2) (m-bcr) encodes a 190 kDa chimeric protein (p190), and in cases of M-bcr, codes a 210 kDa chimeric protein (p210) and in cases of μ-bcr, a 230 kDa protein (p230) (Fausel, 2007). Large studies indicated that BCR-ABL fusion gene is a highly useful diagnostic tool that controls the effectiveness of the chronic myelogenous