Loss of RKIP is a frequent event in MS, both at the protein and mRNA levels. (A) Clinical evaluation of extramedullary involvement in 58 AML patients, who have been analyzed in respect to RKIP protein expression in the leukemic BM previously (cohort I).¹⁵  The frequency of specimens defined as RKIP loss was significantly increased in AML patients with MS compared with those without, as assessed by Fisher’s exact test. (B) RKIP loss was also associated with MS in an independent cohort, where MS was confirmed by biopsy (cohort II). The frequency of RKIP losses was significantly increased in 14 samples of MS compared with 14 specimens of BM from AML patients without any evidence of MS (BM-AML), as calculated by Fisher's exact test. A representative immunohistochemical analysis showing loss of RKIP expression in a specimen of MS and normal RKIP expression in BM-AML is also shown (40× magnification). (C) RKIP mRNA expression analysis by quantitative polymerase chain reaction demonstrating that samples with RKIP loss at the protein level also exhibit decreased levels of RKIP mRNA. NB4 AML cells served as a calibrator, and statistical significance was calculated using the Mann-Whitney-Wilcoxon test.