EXPRESSION OF P53, MDM2, P21(WAF1), BCL-2, AND RETINOBLASTOMA GENE PROTEINS IN MYELODYSPLASTIC SYNDROME AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR LYMPHOMA

Myelodysplastic syndrome (MDS) is an uncommon but serious complication of patients who undergo autologous bone marrow transplantation (auto- BMT) for non-Hodgkin's lymphoma or Hodgkin's disease. Some patients ex hibit an indolent course, but others succumb to aggressive disease. p5 3 overexpression is rare in de novo MDS but common in therapy-associat ed MDS. We used an immunostaining method to analyze expression of p53, the p53-associated tumor suppressor gene products, MDM2, p21(waf1), r etinoblastoma gene protein (pRB), and the antiapoptotic oncoprotein bc l-2 before and after BMT in BM specimens from eight patients with clon al karyotypic abnormalities characteristic of MDS. Staining was compar ed with findings in normal BM specimens and specimens from auto-BMT co ntrols and patients with de novo MDS. p53 protein was found in three ( 75%) of four post-transplantation specimens from patients in whom a cl inically aggressive form of MDS developed. in contrast, p53 was absent in all of the specimens from four patients with karyotypic evidence o f MDS, but with indolent disease. bcl-2 protein was overexpressed by i mmature myeloid cells in seven of eight pre-BMT specimens. After BMT, it tvas predominantly found at low levels in cases positive for p53. M DM2 was present only after transplantation and was found with equal fr equency in patients with indolent and aggressive MDS. We detected p21( waf1) in only one aggressive post-BMT MDS specimen, pRB was normally e xpressed in all of the specimens. These data show that p53 and bcl-2 s taining patterns in post-transplantation MDS are similar to those desc ribed in therapy-associated MDS. p53 positivity is associated with poo r prognosis in auto-BMT patients with MDS. Expression of MDM2, p21(waf 1), and pRB in this group of patients is not helpful in predicting out come.