Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterised by ineffective haematopoiesis. According to the French-American-British (FAB) classification, MDS are subdivided in five groups including refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory anemia with excess of blasts (RAEB), refractory anemia with excess of blasts in transformation (RAEB-t) and chronic myelomonocytic leukemia (CMML). MDS occur predominantly in elderly patients and evolve in acute myeloid leukemia (AML) in about 30% of the cases after variable intervals from diagnosis.1 Recently, Lo Vasco et al2 identified a cryptic deletion of band 20p12.3, involving the Inositide-specific phospholipase c β1 gene (PI-PLC β1), in MDS and AML patients with normal karyotypes. In their series, the deletion was frequent and observed in 33% (2/6) of AML cases and 44% (4/9) of MDS patients. Moreover, the deletion identified a MDS subgroup with normal karyotype and poor prognosis. Patients of this group were at high risk of developing AML with short survival periods (within 1–12 months after developing AML). Search for a deletion of the PI-PLC β1 gene appears thus to be of prognostic importance. However, the number of patients included in the series of Lo Vasco et al2 was low (nine MDS and six AML patients) and, till now, no others studies have confirmed these findings.
In the present report, we assessed the frequency of PI-PLC β1 deletion in 23 MDS and seven AML patients with a normal karyotype at diagnosis (Table 1). FISH investigations were performed with the same probe as in Lo Vasco's study, that is the PAC clone HS881E24 from P de Jong RPCI-5 PAC library. Our series included 17 men and 13 women, aged 25–96 years. The mean age of the MDS and AML populations was, respectively, of 71.9 and 52.2 years (Table 1). Patients no. 1, 12, 20, 21 and 22 developed AML within periods of 6–20 months after the diagnosis. Cytogenetic follow-ups were available for cases no. 11–13, 16, 18 and 20–29. An abnormal karyotype was never identified during follow-ups. Patients no. 18, 21 and 25–29 underwent nonmyeloablative stem cell transplantations.
None of the 23 patients suffering from MDS nor the seven patients with AML had a deletion for the PI-PLC β1 locus when tested by FISH. These results are in contradiction with those of Lo Vasco et al2 as they observed monoallelic deletion of the PI-PLC β1 gene in, respectively, 44 and 33% of the MDS and AML cases. The criteria of selection of our patients were, however, the same as those defined by Lo Vasco, that is, patients with AML or MDS and normal karyotypes at diagnosis. In the same way, the discrepancy between the two studies does not find its origin in the individual prognosis of the patients. In the series of Lo Vasco, six patients, of which four with MDS, had very short survival periods (inferior to 12 months) after diagnosis. All of them showed a deletion of the PI-PLC β1 locus. In our series, five patients developed AML. Three of them evolved rapidly and died within a period of 9–12 months after diagnosis (Table 1). No deletion of the PI-PLC β1 gene was observed in these cases. However, the number of poor prognosis patients is low and does not allow definitive conclusions.
According to our results, systematic investigation of PI-PLC β1 deletions in SMD and AML patients with normal karyotypes is of limited interest. Indeed, PI-PLC β1 deletion appears to be a very rare event (even absent in our series), limiting thus its potential role in the discrimination of a high-risk SMD subgroup with normal karyotype as suggested by Lo Vasco et al.2 Nevertheless, additional reports are needed to determine the exact frequency of PI-PLC β1 deletions in MDS patients.
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Lo Vasco VR, Calabrese G, Manzoli L, Palka G, Spadano A, Morizio E et al. Inositide-specific phospholipase c β1 gene deletion in the progression of myelodysplastic syndrome to acute myeloid leukaemia. Leukemia 2004; 18: 1122–1126.
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Herens, C., Ketelslegers, O., Tassin, F. et al. Inositide-specific phospholipase c β1 gene deletion is a rare event in myelodysplastic syndromes. Leukemia 20, 521–522 (2006). https://doi.org/10.1038/sj.leu.2404109