WPSS is a dynamic prognostic scoring system that provides an accurate prediction of survival and risk of leukemic evolution in MDS patients at any time during the course of their disease. This time-dependent system seems particularly useful in lower risk patients and may be used for implementing risk-adapted treatment strategies.

These data show that the WHO classification of MDSs has a relevant prognostic value. This classification, along with cytogenetics, might be useful in decisions regarding transplantation. MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable.

Ferritin is a ubiquitous protein that plays a critical role in regulating intracellular iron homoeostasis by storing iron inside its multimeric shell. It also plays an important role in detoxifying potentially harmful free ferrous iron to the less soluble ferric iron by virtue of the ferroxidase activity of the H subunit. Although excess iron is stored primarily in cytoplasm, most of the metabolically active iron in cells is processed in mitochondria. Little is yet known of how these organelles regulate iron homeostasis and toxicity. Here we report an unusual intronless gene on chromosome 5q23.1 that encodes a 242-amino acid precursor of a ferritin H-like protein. This 30-kDa protein is targeted to mitochondria and processed to a 22-kDa subunit that assembles into typical ferritin shells and has ferroxidase activity. Immunohistochemical analysis showed that it accumulates in high amounts in ironloaded mitochondria of erythroblasts of subjects with impaired heme synthesis. This new ferritin may play an important role in the regulation of mitochondrial iron homeostasis and heme synthesis.

The WHO recently proposed a new classification of myelodysplastic syndromes (MDS) based on uni- or multi-lineage hematopoietic involvement, blast count and cytogenetic features. The aims of this study were to evaluate the prognostic value of the WHO classification, to assess the role of known prognostic factors in MDS within these WHO subgroups, and to estimate mortality rates and life expectancy of the patients in the subgroups. Four hundred and ninety-one consecutive patients with a diagnosis of MDS made at the IRCCS Policlinico San Matteo, University of Pavia Medical School, Italy, between 1992 and 2002 were retrospectively evaluated and reclassified according to the WHO criteria. Cox proportional hazards regression was used to identify the most significant prognostic factors. A standardized mortality ratio (SMR) was calculated to compare the mortality of MDS patients with that of the general population. Overall survival (OS) and leukemia-free survival (LFS) differed significantly between RA and RCMD (P<.001 and P=.01, respectively), but not between RA and MDS with del(5q), or between MDS with or without ringed sideroblasts. There was a significant difference in LFS between RCMD and RAEB-1 (P=.006), and in both OS and LFS between RAEB-1 and -2 (P<.001). Overall, age and gender had significant effects on survival (P<.001), older age and male gender negatively affecting the prognosis. These effects were statistically significant for RA and RCMD patients (P values from.01 to <.001), but not for those with RAEB. The mortality rate of all patients with RA/RARS aged 70 years or older and the male subgroup aged 65-70 years old did not differ from that of the general population. Cox regression analysis with time dependent covariates was applied to evaluate the prognostic value of needing transfusion. Patients with RA/RARS who became transfusion-dependent had a significantly shorter life expectancy than those who did not (P=.01) except for patients aged 70 years or older whose life expectancy was only marginally shorter than that of the general population (SMR=1.90, P=.03). Cox regression showed that IPSS significantly stratified OS and LFS of WHO subgroups (P=.005 and P=.003, respectively). Among IPSS variables, blast count and peripheral cytopenia failed to predict survival within the WHO subgroups, while karyotypic abnormalities, classified according to IPSS, significantly affected OS and LFS of MDS stratified in WHO categories (P=.03 and P=.02, respectively). In conclusion, the new WHO classification of MDS has relevant prognostic value. Cytogenetics is the only independent prognostic factor significantly affecting survival of patients classified into these WHO subgroups. MDS with uni-lineage dysplasia identifies a subset of truly low risk patients, whose survival is significantly affected by demographic characteristics. Patients with refractory anemia who are older than 70 years, as well the males aged between 65 and 70 years, have a life expectancy similar to that of the general population, and only slightly worsened by becoming transfusion-dependent. According to these results, extending curative approaches, such as non-myeloablative transplantation, to these groups of patients does not seem advisable.