We prospectively examined whether surface expression of Cytokine Receptor-Like Factor 2 (CRLF2) on leukemic blasts is associated with survival and induction treatment response in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Flow cytometric analysis of bone marrow-derived leukemia cells revealed that 7.51% (29/286) of 386 pediatric BCP-ALL patients were CRLF2-positive (CRLF2pos) at diagnosis. The median minimal residual disease (MRD) was lower in CRLF2pos than CRLF2-negative (CRLF2neg) patients on day 15 (MRD15) after induction therapy 0.01% (0.001-0.42%) vs. 0.45% (0.05-3.50%); p=0.001. By contrast, the MRD15 was higher in Ikaros family Zinc Finger Protein 1 ( -deleted BCP-ALL patients than in BCP-ALL patients without deletions 1.18% (0.06-12.0%) vs 0.33% (0.03-2.6%); p=0.003. Subgroup analysis showed that MRD15 levels were lower in /CRLF2pos patients than in /CRLF2neg patients 0.1% (0.02-5.06%) vs. 2.9% (0.25-12%); p=0.005. Furthermore, MRD15 levels were higher in WT/CRLF2neg patients than in WT/CRLF2pos patients 0.40% (0.04-2.7%) vs. 0.001% (0.001-0.01%). Despite the low MRD15 levels, Δ/CRLF2pos patients showed poorer relapse-free survival (RFS) than other patient groups (p=0.003). These findings demonstrate that surface CRLF2 expression is associated with increased risk of relapse in pediatric BCP-ALL patients harboring deletions.