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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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 2

Patterns of genomic evolution from diagnosis to relapse in ALL.

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Patterns of genomic evolution from diagnosis to relapse in ALL. Leukemic...
Leukemic clones at relapse are frequently related to leukemic clones present at diagnosis. In more than half of cases, the relapse clone arises from a clone present prior to diagnosis, retaining some but not all of the lesions found at diagnosis and containing some additional mutations. The relapse clone is often present as a rare subclone within the diagnostic sample. Alternatively, cases of relapse can stem from the diagnosis clone, acquiring additional mutations. Less commonly, the relapse clone may be identical to the diagnosis clone or appear to be an unrelated second leukemia.