Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications

Sabina Chiaretti*, Monica Messina, Sara Grammatico, Alfonso Piciocchi, Anna L. Fedullo, Filomena Di Giacomo, Nadia Peragine, Valentina Gianfelici, Alessia Lauretti, Rohan Bareja, Maria P. Martelli, Marco Vignetti, Valerio Apicella, Antonella Vitale, Loretta S. Li, Cyril Salek, Olivier Elemento, Giorgio Inghirami, David M. Weinstock, Anna GuariniRobin Foà

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values – assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical “BCR/ABL1-like predictor”, for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the “BCR/ABL1-like predictor”, we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis.

Original languageEnglish (US)
Pages (from-to)642-652
Number of pages11
JournalBritish Journal of Haematology
Volume181
Issue number5
DOIs
StatePublished - Jun 2018

Keywords

  • Acute lymphoblastic leukaemia
  • BCR/ABL1-like
  • adults
  • prognosis
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Hematology

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