Deletion of Tumor Suppressor Genes (TSGS) in Patients with Myelodysplastic Syndrome (MDS).

Background: The deletion of genomic sites harboring TSGs is known to be a powerful prognostic indicator in various chronic hematologic malignancies. However, the clinical significance of TSGs loss in MDS has not been thoroughly investigated.

Aims: To summarize our experience on the incidence and essential clinical correlates of TSGs deletions in MDS, providing preliminary results from the study of 27 patients.

Methods: The study included 17 men and 10 women (median age 74; range 38–84 years) with a documented diagnosis of MDS. The distribution of FAB subtypes was RA in 13, RARS in 3, RAEB in 6, RAEB-T in 4 and CMML in 1 case. According to the IPSS stratification, 5 patients were characterized as “low-risk”, 16 as “intermediate-risk” (11 as INT-1 and 5 as INT-2) and 6 as “high-risk” patients. The diagnostic bone marrow smears were studied with fluorescence in-situ hybridization (FISH) for deletions of chromosome regions 9p21 (p16/p14 and p15 genes), 9q34, 12p13 (TEL gene), 13q14 (RB1 gene D13S319 locus) and 17p13 (p53 gene).

Results: A deletion in at least one of the chromosome regions or loci studied was detected in 10 patients (37%). In 6 of them, more than one region locus was lost, making up a total of 20 deletions. The commonest finding was loss of the 17p13 region (5 cases; two of them homozygous), followed by 9p21 loss (5 cases; one of them homozygous). Overall, the presence of TSGs deletions was associated with complex karyotype, high IPSS score and risk of death (regardless of leukemic progression). Interestingly, deletion in at least one of the TSGs studied was found in 5 of the 17 patients presenting with normal karyotype. In 3 of these patients, the MDS progressed to acute leukemia. Two of the 5 patients died at one and six months from diagnosis of the MDS, without leukemic conversion.

Summary/Conclusions: Deletions of TSGs are not uncommon in MDS. Interestingly, we have found that certain TSGs, such as the p16/p14 and p15 genes at 9p21, the loss of which is mostly involved in the initiation or progression of lymploid neoplasms, are also frequently deleted in MDS. Overall, TSGs deletion in this small group of patients is apparently associated with other adverse biological and clinical features and poor outcome. Therefore, these preliminary observations justify the expansion of the study in a larger patient cohort, in order to clarify if the loss of certain TSGs is an independent prognostic factor in MDS and, thus, may be of help in the initial diagnostic approach and risk stratification of the patients.