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.

TitleRapid 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.
Publication TypeJournal Article
Year of Publication2018
AuthorsChiaretti S, Messina M, Grammatico S, Piciocchi A, Fedullo AL, Di Giacomo F, Peragine N, Gianfelici V, Lauretti A, Bareja R, Martelli MP, Vignetti M, Apicella V, Vitale A, Li LS, Salek C, Elemento O, Inghirami G, Weinstock DM, Guarini A, Foà R
JournalBr J Haematol
Volume181
Issue5
Pagination642-652
Date Published2018 06
ISSN1365-2141
KeywordsAdolescent, Adult, Child, Child, Preschool, Disease-Free Survival, Female, Fusion Proteins, bcr-abl, Gene Expression Regulation, Leukemic, Humans, Infant, Infant, Newborn, Male, Models, Biological, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Predictive Value of Tests, Real-Time Polymerase Chain Reaction, Survival Rate
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.

DOI10.1111/bjh.15251
Alternate JournalBr. J. Haematol.
PubMed ID29675955
PubMed Central IDPMC5975184
Grant ListR01 AA017238 / AA / NIAAA NIH HHS / United States
R01 CA151898 / CA / NCI NIH HHS / United States
R01 CA194547 / CA / NCI NIH HHS / United States