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B lymphoblastic leukemia/lymphoma: new insights into genetics, molecular aberrations, subclassification and targeted therapy
Journal article   Open access   Peer reviewed

B lymphoblastic leukemia/lymphoma: new insights into genetics, molecular aberrations, subclassification and targeted therapy

Xiaohui Zhang, Prerna Rastogi, Bijal Shah and Ling Zhang
Oncotarget, Vol.8(39), pp.66728-66741
2017
DOI: 10.18632/oncotarget.19271
PMCID: PMC5630450
PMID: 29029550
url
https://doi.org/10.18632/oncotarget.19271View
Published (Version of record) Open Access

Abstract

B lymphoblastic leukemia/lymphoma (B-ALL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mostly occurs in children and adolescents and is regarded as one of top leading causes of death related to malignancies in this population. Despite the majority of patients with B-ALL have fairly good response to conventional chemotherapeutic interventions followed by hematopoietic stem cell transplant for the last decades, a subpopulation of patients show chemo-resistance and a high relapse rate. Adult B-ALL exhibits similar clinical course but worse prognosis in comparison to younger individuals. Ample evidences have shown that the clinical behavior, response rate and clinical outcome of B-ALL rely largely on its genetic and molecular profiles, such as the presence of BCR-ABL1 fusion gene which is an independent negative prognostic predictor. New B-ALL subtypes have been recognized with recurrent genetic abnormalities, including B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21), B-ALL with translocations involving tyrosine kinases or cytokine receptors (“BCR-ABL1-like ALL”). Genome-wide genetic profiling studies on B-ALL have extended our understanding of genomic landscape of B-ALL, and genetic mutations involved in various key pathways have been illustrated. These include CRLF2 and PAX5 alterations , TP53, CREBBP and ERG mutations, characteristic genetic aberrations in BCR-ABL1-like B-ALL and others. The review further provides new insights into clinical implication of the genetic aberrations in regard to targeted therapy development.
Genetics Molecular Biology B lymphoblastic leukemia lymphoma predictive markers prognostic markers Review

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