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New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

Lookup NU author(s): Professor Anthony Moorman

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Abstract

A cute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1 and high hyperdiploidy are good-risk prognostic biomarkers whereas KMT2A (MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are highrisk biomarkers. t(9;22)/BCR-ABL1 patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes - ABL1, ABL2, PDGFRB, CSF1R, CRLF2, JAK2 and EPOR. In vitro and in vivo studies along with emerging clinical observations indicate that patients with a kinase activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL.


Publication metadata

Author(s): Moorman AV

Publication type: Review

Publication status: Published

Journal: Haematologica

Year: 2016

Volume: 101

Issue: 4

Pages: 407-416

Print publication date: 01/04/2016

Acceptance date: 25/01/2016

ISSN (print): 0390-6078

Publisher: FERRATA STORTI FOUNDATION

URL: http://dx.doi.org/10.3324/haematol.2015.141101

DOI: 10.3324/haematol.2015.141101


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