title: New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia.
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.
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK anthony.moorman@newcastle.ac.uk.
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D000069439:Dasatinib / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D009570:Nitriles; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines; D016019:Survival Analysis; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009570:Nitriles; D015514:Oncogene Proteins, Fusion; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D000068877:Imatinib Mesylate; D000069439:Dasatinib