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Design of a Comprehensive Fluorescence in Situ Hybridization Assay for Genetic Classification of T-Cell Acute Lymphoblastic Leukemia

Lookup NU author(s): Claire Schwab, Professor Christine Harrison FRCPath FMedSci


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© 2020 Association for Molecular Pathology and American Society for Investigative PathologyT-cell acute lymphoblastic leukemia (T-ALL) results from deregulation of a number of genes via multiple genomic mechanisms. We designed a comprehensive fluorescence in situ hybridization (CI-FISH) assay that consists of genomic probes to simultaneously investigate oncogenes and oncosuppressors recurrently involved in chromosome rearrangements in T-ALL, which was applied to 338 T-ALL cases. CI-FISH provided genetic classification into one of the well-defined genetic subgroups (ie, TAL/LMO, HOXA, TLX3, TLX1, NKX2-1/2-2, or MEF2C) in 80% of cases. Two patients with translocations of the LMO3 transcription factor were identified, suggesting that LMO3 activation may serve as an alternative to LMO1/LMO2 activation in the pathogenesis of this disease. Moreover, intrachromosomal rearrangements that involved the 10q24 locus were found as a new mechanism of TLX1 activation. An unequal distribution of cooperating genetic defects was found among the six genetic subgroups. Interestingly, deletions that targeted TCF7 or TP53 were exclusively found in HOXA T-ALL, LEF1 defects were prevalent in NKX2-1 rearranged patients, CASP8AP2 and PTEN alterations were significantly enriched in TAL/LMO leukemias, and PTPN2 and NUP214-ABL1 abnormalities occurred in TLX1/TLX3. This work convincingly shows that CI-FISH is a powerful tool to define genetic heterogeneity of T-ALL, which may be applied as a rapid and accurate diagnostic test.

Publication metadata

Author(s): La Starza R, Pierini V, Pierini T, Nofrini V, Matteucci C, Arniani S, Moretti M, Lema Fernandez AG, Pellanera F, Di Giacomo D, Storlazzi TC, Vitale A, Gorello P, Sammarelli G, Roti G, Basso G, Chiaretti S, Foa R, Schwab C, Harrison CJ, Van Vlierberghe P, Mecucci C

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Diagnostics

Year: 2020

Volume: 22

Issue: 5

Pages: 629-639

Print publication date: 01/05/2020

Online publication date: 03/03/2020

Acceptance date: 03/02/2020

ISSN (print): 1525-1578

ISSN (electronic): 1943-7811

Publisher: Elsevier


DOI: 10.1016/j.jmoldx.2020.02.004

PubMed id: 32142900


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