Expression of p53, MDM2, p21waf1, 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 exhibit an indolent course, but others succumb to aggressive disease. p53 overexpression is rare in de novo MDS but common in therapy-associated MDS. We used an immunostaining method to analyze expression of p53, the p53-associated tumor suppressor gene products, MDM2, p21waf1, retinoblastoma gene protein (pRB), and the antiapoptotic oncoprotein bcl-2 before and after BMT in BM specimens from eight patients with clonal karyotypic abnormalities characteristic of MDS. Staining was compared with findings in normal BM specimens and specimens from auto-BMT controls and patients with de novo MDS. p53 protein was found in three (75%) of four post-transplantation specimens from patients in whom a clinically aggressive form of MDS developed. In contrast, p53 was absent in all of the specimens from four patients with karyotypic evidence of MDS, but with indolent disease. bcl-2 protein was overexpressed by immature myeloid cells in seven of eight pre-BMT specimens. After BMT, it was predominantly found at low levels in cases positive for p53. MDM2 was present only after transplantation and was found with equal frequency in patients with indolent and aggressive MDS. We detected p21waf1 in only one aggressive post-BMT MDS specimen. pRB was normally expressed in all of the specimens. These data show that p53 and bcl-2 staining patterns in post-transplantation MDS are similar to those described in therapy-associated MDS. p53 positivity is associated with poor prognosis in auto-BMT patients with MDS. Expression of MDM2, p21waf1, and pRB in this group of patients is not helpful in predicting outcome.
Brynes
R K
RK
Department of Clinical Pathology, City of Hope National Medical Center, Duarte, California 91010, USA. Rbrynes@smtplink.coh.org
Wilson
C S
CS
Kim
A B
AB
McCourty
A
A
D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D006689:Hodgkin Disease / Q000473:pathology / Q000628:therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008223:Lymphoma / Q000473:pathology / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014182:Transplantation, Autologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2