Rapid identification of BCR / ABL 1 BCR BCR / ABL ABL 1 ‐like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time‐polymerase chain reaction: clinical, prognostic and therapeutic implications

摘要

Summary BCR / ABL 1 ‐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 / ABL 1 ‐like ALL cases and used their expression values – assessed by quantitative real time‐polymerase chain reaction (Q‐ RT ‐ PCR ) in 26 BCR / ABL 1 ‐like and 26 non‐ BCR / ABL 1 ‐like cases to build a statistical “ BCR / ABL 1 ‐like predictor”, for the identification of BCR / ABL 1 ‐like cases. By screening 142 B‐lineage ALL patients with the “ BCR / ABL 1 ‐like predictor”, we identified 28/142 BCR / ABL 1 ‐like patients (19·7%). Overall, BCR / ABL 1 ‐like cases were enriched in JAK / STAT mutations ( P? ? 0·001), IKZF 1 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 / ABL 1 ‐like cases identified by the BCR / ABL 1 ‐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 / ABL 1‐ like ALL . Consistently, primary cells from BCR / ABL 1 ‐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 / ABL 1 ‐like ALL cases at diagnosis.