ALBERT

Description: Myelodysplastic syndrome (MDS) is a group of hematopoietic stem/progenitor cell clonal disorders characterized by dysplastic morphology of at least one cell lineage and high risk of evolution to acute myeloid leukemia (AML). Thus, it could be viewed as a preneoplastic stage prior to development of overt acute myeloid leukemia (AML). A number of studies indicated that oncogene-induced senescence as a crucial cellular response at premalignant stage can protect cells from tumor formation. Senescent cells emerged in premalignant cell population but not in malignant ones. p16INK4a have been identified as a cellular senescence-associated molecular marker. In present study, we have determined and compared the expression level of p16INK4a by quantitative RT-PCR and western blot in BM mononuclear cells (BMMNCs)/CD34+ cells among 53 patients of MDS and 12 of AML as well as 11 healthy controls. A significantly upregulated expression level of p16INK4a in MDS, while an significantly lower p16INK4a expression level in AML had been detected in comparison with that in healthy controls(

Description: Abstract 4858 Objective To determining the clonal origin of dysplatic cells in Myelodysplastic syndromes (MDS) . Methods Karyotypic analyses of bone marrow cells using R-banding technique were carried out to determine the chromosomal abnormalities. Interphase fluorescence in situ hybridization (FISH) and morphologic analysis of bone marrow aspirates were performed in the same cells to investigate the clonal origin of dysplatic cells in 8 MDS patients. Result All patients had clonal karyotypic abnormalities: simple abnormality in 1 patient, complex abnormalities in 6 patients, coexistent of two unrelated clones in 1 patient. Most of dysplastic cells in 7 of 8 MDS patients derived from neoplasia clone while 1 patient had a reverse result,no matter what cell lineage was involved. Some of non-dysplastic cells of all patients derived from malignant clone; in 7 patients, the proportion of dysplastic cells in malignant clone were significantly higher than that of non- malignant clone. Conclusion Most of dysplastic cells in MDS derived from malignant clones, while the minority of them derived from non-malignant clones. Thus, it is reasonable to expect that in most cases myelodysplasia is present in malignant clone and can be taken as an important diagnostic evidence for MDS. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4242 A pericentric inversion(9)(p21q34) was identified in five Ph-positive leukemia patients including four patients with chronic myeloid leukemia(CML) in chronic phase(CP) and one patient with acute myeloid leukemia (AML) since 1998. Among them, two were males, three wrer females. The median age is 31 years (range 21-52 years). Conventional karyotypic analysis with R-banding technique showed that the inv(9)(p21q34) always occurred in the der(9)t(9;22)(q34;q11) and was accompanied by the der(22)t(9;22)(q34;q11) in all metaphases analyzed in four patients with CML-CP at diagnosis. One patient with AML presented three clones: one with normal karyotype, one with sole t(9;22)(q34;q11), one with inv(9)(p21q34) involving the der(9)t(9;22) and additional t(8;12)(q12;p11). FISH using LSI BCR/ABL dual-color, dual fusion probe, chromosome painting(CP) with the paint probes for chromosome 9p and 9q and RT-PCR using the primers of the BCR/ABL fusion genes were performed in four of them. FISH showed the coexistence of clone with sole t(9;22) and another with inv(9)(p11q34) and t(9;22) in four patients in whom, one patient also showed a deletion of partial sequence from BCR on der(9)t(9;22)inv(9)(p21q34). RT-PCR revealed a b3a2 transcript for BCR/ABL fusion gene transcript. FISH proved that the inv(9)(p21q34) disrupted the ABL/BCR fusion gene at the molecular level. However, it does not appear to have any biological significance because BCR/ABL fusion gene is thought to be involved in the pathogenesis of CML, while ABL/BCR fusion gene is merely mechanical consequence of the t(9;22) translocation. As far as we know, inv(9)(p21q34) has not been reperted previously. Thus, it should be regarded as a novel rare but recurrent secondary chromosomal anomaly. In this series, one lost to follow-up, one patient transformed into B cell acute lymphocytic leukemia, who and other two patients survivals of 28 days, 13 and 34 months, respectively. Only one remains alive. Their dismal outcome probably suggests inv(9)(p21q34) having unfavourable impact on prognosis. At present, no firm conclusion can be drawn from this study. More patients with this anomaly need to be investigated to elucidate its prognostic significance. Disclosures: No relevant conflicts of interest to declare.