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Review
. 2016 Apr;101(4):407-16.
doi: 10.3324/haematol.2015.141101.

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

Anthony V Moorman  1
Affiliations
Review

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

Anthony V Moorman. Haematologica. 2016 Apr.

Abstract

Acute 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 hyper-diploidy are good-risk prognostic biomarkers whereas KMT2A(MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are high-risk 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.

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Figures

Figure 1.
Figure 1.
Overview of key co-operating mutations in relation to distinct genetic subtypes of B-cell precursor acute lympholastic leukemia.
Figure 2.
Figure 2.
Frequency of primary chromosomal abnormalities in children and adults with B-cell precursor acute lymphoblastic leukemia.
Figure 3.
Figure 3.
Outcome of patients with acute lymphoblastic leukemia (ALL) by genetic risk group. (A) Event-free survival of children and adolescents with B-cell precursor ALL treated on ALL2003 and stratified by cytogenetics and copy number alterations profile. (B) Survival of adults treated on UKALLXII stratified by genetic risk group.
Figure 4.
Figure 4.
Proposal for a new integrated risk classification of childhood B-cell precursor acute lymphoblastic leukemia based on primary chromosomal abnormalities and copy number alteration (CNA) profile (yellow indicates deleted; blue indicates not deleted).
See this image and copyright information in PMC

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