Advances in B-lymphoblastic leukemia: Cytogenetic and genomic lesions

Abstract The genomic profiling of B-cell lymphoblastic leukemia (B-ALL) subtypes are characterized by a constellation of genetic changes involving structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations. Several of these genetic changes have relevant implication...

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Bibliographic Details
Published in:Annals of diagnostic pathology 2016-08, Vol.23, p.43-50
Main Authors: Zhou, Yi, MD, PhD, Kanagal-Shamanna, Rashmi, MD, Zuo, Zhuang, MD, Tang, Guilin, MD, PhD, Medeiros, L. Jeffrey, MD, Bueso-Ramos, Carlos E., MD, PhD
Format: Article
Language:English
Subjects:
B-cell development
B-cell lymphoblastic leukemia
B-Lymphocytes - cytology
Clonal evolution
Gene Expression Regulation, Neoplastic - genetics
Genetic Predisposition to Disease
Genome, Human
Genomic
Genomics
Humans
Leukemia, B-Cell - diagnosis
Leukemia, B-Cell - genetics
Leukemia, B-Cell - pathology
Molecular pathology
Pathology
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Summary:Abstract The genomic profiling of B-cell lymphoblastic leukemia (B-ALL) subtypes are characterized by a constellation of genetic changes involving structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations. Several of these genetic changes have relevant implications for risk stratification and targeted therapeutic interventions. In this review, we summarize some of the well-known and recently identified genomic risk factors for B-ALL, with emphasis on their associated prognoses and methods of detection. Alterations in genes that regulate B-cell development are hallmarks of B-ALL. In particular, deletions of IKZF1 , a gene determining early lymphoid differentiation, are associated with high risk Ph + and Ph-like B-ALL subtypes. About 20% of B-ALL patients harbor genetic alterations that result in aberrant activation of protein tyrosine kinases. The genetic alterations include rearrangements of the cytokine receptor gene CRLF2 ; rearrangements of ABL1 , JAK2 , and PDGFRB ; and mutations of JAK1 and JAK2. B-ALL with these genetic alterations may respond to targeted therapy using tyrosine kinase inhibitors. Recurrent genetic alterations involving TP53 , CREBBP , and NT5C2 are enriched in relapsed B-ALL and may confer drug resistance. Future challenges include implementing genomic profiling into the clinic to guide risk stratification and the use of targeted therapies.
ISSN:1092-9134
1532-8198
DOI:10.1016/j.anndiagpath.2016.02.002