Co-occurring low expression of miR-497/195 and deletion of CDKN2A and CDKN2B are associated with inferior patient outcome. (A) TTL (weeks) for NOD/SCID mice transplanted with patient samples, grouped according to miR-497/195 expression and CDKN2A and CDKN2B deletion. Low miR-497/195, CDKN2A/B del: expression of miR-497/195 (log₁₀ miR-497 + log₁₀ miR-195) was below median; homozygous deletion of both CDKN2A and CDKN2B. Others includes samples with expression of miR-497/195 above median and/or heterozygous deletion or full sequence of CDKN2A, CDKN2B, or both. (B) Relapse-free survival (months) of patients who relapsed in the pdx cohort, grouped according to expression of miR-497/195 and deletion of CDKN2A and CDKN2B in the respective pdx samples (panel A). (C) Relapse-free survival (years) for patients from an independent cohort of diagnostic BCP-ALL samples, grouped according to expression of miR-497/195 and deletion of CDKN2A and CDKN2B. Low miR-497/195, CDKN2A/B del: expression of miR-497/195 was below median; homozygous deletion of both CDKN2A and CDKN2B. Others includes samples with expression of miR-497/195 above median and/or full sequence of CDKN2A and CDKN2B. (D) Relapse-free survival (years) of patients in panel C. Low miR-497/195, CDKN2A/B del: expression of miR-497/195 was below median; homozygous deletion of both CDKN2A and CDKN2B. High miR-497/195, CDKN2A/B non-del: expression of miR-497/195 was above median; full sequence of both CDKN2A and CDKN2B. Others are samples with high expression of miR-497/195 and deletion of CDKN2A and CDKN2B or low expression of miR-497/195 and full sequence of CDKN2A and CDKN2B. Mean survival [%] ± SEM is indicated. Log-rank test was used for data analysis. (E) Proposed mechanism of enhanced leukemia growth upon co-occurring low expression of miR-497/195 and deletion of CDKN2A and CDKN2B.