Molecular genetics of B-precursor acute lymphoblastic leukemia
Charles G. Mullighan
Charles G. Mullighan
Published October 1, 2012
Citation Information: J Clin Invest. 2012;122(10):3407-3415. https://doi.org/10.1172/JCI61203.
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Category: Review Series

Molecular genetics of B-precursor acute lymphoblastic leukemia

Abstract

B-precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood tumor and the leading cause of cancer-related death in children and young adults. The majority of B-ALL cases are aneuploid or harbor recurring structural chromosomal rearrangements that are important initiating events in leukemogenesis but are insufficient to explain the biology and heterogeneity of disease. Recent studies have used microarrays and sequencing to comprehensively identify all somatic genetic alterations in acute lymphoblastic leukemia (ALL). These studies have identified cryptic or submicroscopic genetic alterations that define new ALL subtypes, cooperate with known chromosomal rearrangements, and influence prognosis. This article reviews these advances, discusses results from ongoing second-generation sequencing studies of ALL, and highlights challenges and opportunities for future genetic profiling approaches.

Authors

Charles G. Mullighan

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Figure 1

Frequency of cytogenetic subtypes of pediatric ALL.

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Frequency of cytogenetic subtypes of pediatric ALL. The pie chart includ...
The pie chart includes all major B-ALLs and T-lineage subtypes of ALL, to illustrate the relative frequency of each. The recently described BCR-ABL1–like subtype and BCR-ABL1–positive ALL are shown in yellow to illustrate the high frequency of childhood B-ALL cases with genetic alterations activating tyrosine kinase and cytokine receptor signaling that may be amenable to targeted therapy. Data are derived from front-line studies of childhood ALL (121).