WT-1 Over-Expression Could Be Related to " High Metaplastic Index" in Myelofibrosis with Myeloid Metaplasia (MMM) Patients. A Preliminary Report.

WT1 is a tumor-suppressor gene coding for a zinc-finger transcription factor located on chromosome 11p13, which was originally identified for its involvement in the pathogenesis of the Wilms’ tumor. In normal bone marrow and peripheral blood(PB)WT1 expression is extremely low and often undetectable even by RT-PCR. By contrast WT1 expression has been previously reported to be increased in MDS, AML, ALL and PNH. In CMPDs, little data are available only in CML. With this background we analyze by RQ-PCR the WT1 transcript amount in 13 patients with myelofibrosis with myeloid metaplasia (MMM) in comparison with a group of 32 age- and sex-matched healthy controls. All measurements were carried out only on PB and performed as previous published. All MMM patients were under cytoreductive treatment and at different time from diagnosis ( range 1 – 7 yrs). In MMM WT1 transcript amount is consistently higher (range 23–2518 WT1 copies/10⁴ ABL copies, mean 382±692) than controls ( range 0 – 22, mean 5,6 ± 5,87) ( P < 0.0001 Mann-Whitney U test). To assess the significance of the WT1 expression as a marker for disease features, the following variables were analyzed and compared : age, hemoglobin level, white blood cell count, circulating blasts, LDH serum levels, number of peripheral CD 34 cells, Dupriez score and, according to Barosi published data, myeloproliferation index, myelodepletion index, severity score. We did not found any significant correlation between WT1 and all these variables, probably because the patients were studied during the course of their disease. Moreover, cytoreductive treatment might have modified the disease characteristics. Stricking, when analyzed WT1 expression according to the therapeutic need, we found a subset of patients with a WT1 overexpression ( range 132–2518, mean 758±911; p <0.06) and spleen size between 4 – 7 cm despite receiving > 1,5 gr/daily of hydroxyurea or more than 1 drug. In such of patients WT1 over-expression allowed an almost complete discrimination between MMM in stable phase and MMM with “high metaplastic index”. In conclusion, our results, although based on a relatively small number of patients, provide an interesting profile of WT1 expression in MMM. The possible clinico-therapeutic implications of these observations are worthy of investigation in well-designed studies.