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

Research output: Contribution to journalReview article

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 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 kinaseactivating 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.

Original languageEnglish (US)
Pages (from-to)407-416
Number of pages10
JournalHaematologica
Volume101
Issue number4
DOIs
StatePublished - Mar 31 2016
Externally publishedYes

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B-Lymphoid Precursor Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Biomarkers
Platelet-Derived Growth Factor beta Receptor
Inborn Genetic Diseases
Polyploidy
Gene Regulatory Networks
Gene Fusion
Haploidy
Transcriptome
Chromosome Aberrations
Phosphotransferases
Technology
Therapeutics
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Hematology

Cite this

New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia. / Moorman, Anthony.

In: Haematologica, Vol. 101, No. 4, 31.03.2016, p. 407-416.

Research output: Contribution to journalReview article

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