Abstract
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with the majority of cases being of precursor B-cell phenoltype. Conventional cytogenetic analysis plays an important role in the diagnosis of B-cell ALL, identifying characteristic chromosomal abnormalities associated with a given prognosis therein facilitating optimized treatment. The more recent introduction of microarray technology to the analysis of B-cell ALL has afforded both higher resolution for the detection of known abnormalities and an ability to identify novel copy number abnormalities (CNAs) with potential clinical relevance. In the current study, microarray analysis was performed on 20 cytogenetically abnormal B-cell ALL cases (10 pediatric and 10 adult), while a novel microarray-based balanced-translocation detection methodology (translocation CGH or tCGH) was applied to that subset of cases with a known or suspected recurrent balanced translocation. Standard microarray analysis identified that CNAs was not detected by previous conventional cytogenetics in 75% (15/20) cases. tCGH identified 9/9 (100%) balanced translocations defining BCR/ABL1 (x4), ETV6/RUNX1 (x3), and MLL/AFF1 (x2) breakpoints with high resolution. The results illustrate the improved molecular detail afforded by these technologies and a comparison of translocation breakpoints, CNAs and patient age offers new insights into tumor biology with potential prognostic significance.
Highlights
B-cell acute lymphoblastic leukemia (B-cell Acute lymphoblastic leukemia (ALL)) is the most common pediatric malignancy
Case 10, which revealed a breakpoint for a genomic copy gain by aCGH, did not exhibit any translocation when analyzed with the translocation CGH array (tCGH) assay
Conventional cytogenetics has been the standard of care for the identification of diagnostically and prognostically significant genomic alterations in ALL, despite the inherent challenge posed by these cases due to poor chromosome morphology
Summary
B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common pediatric malignancy. Conventional cytogenetic analysis has been an integral part of the evaluation of B-cell ALL, influencing prognosis and treatment decisions [6,7]. Specific cytogenetic findings, such as the t (9;22) (q34;q11.2) resulting in BCR/ABL1 fusion, MLL OPEN ACCESS. Hyperdiploidy, involving gains of chromosomes 4 and 10, and the t (12;21) (p13;q22) resulting in ETV6/RUNX1 fusion, are associated with a good prognosis [8]. Some cases of B-cell ALL lack alterations detectable by conventional cytogenetics and, importantly, some patients with favorable cytogenetic alterations still relapse, which may indicate that that there are additional undetected chromosome aberrations [9]
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