After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.

BACKGROUND: Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low‐risk patients remains controversial. METHODS: The authors analyzed the incidence and prognostic significance of thrombocytopenia at diagnosis in 2565 de novo MDS patients included in the Spanish MDS Registry. RESULTS: Thrombocytopenia (platelet count <100 × 109/L) was identified in 842 patients (32.8%). Severe thrombocytopenia (platelet count <30 × 109/L) was observed in 7.1% of patients and was significantly associated with a higher‐risk World Health Organization subtype (P = .026) and intermediate‐2/high‐risk International Prognostic Scoring System (IPSS) score (P = .046). Severe thrombocytopenia was the most important prognostic factor and had negative effects on the low/intermediate‐1 risk group. Median overall survival of patients with a platelet count <30 and ≥30 × 109/L was 16 months and 71 months, respectively (hazard ratio, 4.66; 95% confidence interval, 2.74‐7.90; P < .0001). The negative effect of severe thrombocytopenia in low/intermediate‐1 risk patients was caused by increased risk of bleeding. CONCLUSIONS: MDS patients with low/intermediate‐1 IPSS risk score and severe thrombocytopenia should no longer be regarded as low risk, and must be considered for disease‐altering approaches at diagnosis. Cancer 2011;. © 2011 American Cancer Society.

BackgroundChronic Lymphocytic Leukemia (CLL) leads to progressive accumulation of lymphocytes in the blood, bone marrow, and lymphatic tissues. Previous findings have suggested that the mtDNA could play an important role in CLL.Methodology/Principal FindingsThe mitochondrial DNA (mtDNA) control-region was analyzed in lymphocyte cell DNA extracts and compared with their granulocyte counterpart extract of 146 patients suffering from B-Cell CLL; B-CLL (all recruited from the Basque country). Major efforts were undertaken to rule out methodological artefacts that would render a high false positive rate for mtDNA instabilities and thus lead to erroneous interpretation of sequence instabilities. Only twenty instabilities were finally confirmed, most of them affecting the homopolymeric stretch located in the second hypervariable segment (HVS-II) around position 310, which is well known to constitute an extreme mutational hotspot of length polymorphism, as these mutations are frequently observed in the general human population. A critical revision of the findings in previous studies indicates a lack of proper methodological standards, which eventually led to an overinterpretation of the role of the mtDNA in CLL tumorigenesis.Conclusions/SignificanceOur results suggest that mtDNA instability is not the primary causal factor in B-CLL. A secondary role of mtDNA mutations cannot be fully ruled out under the hypothesis that the progressive accumulation of mtDNA instabilities could finally contribute to the tumoral process. Recommendations are given that would help to minimize erroneous interpretation of sequencing results in mtDNA studies in tumorigenesis.

Genome wide association studies (GWAS) have identified several low-penetrance susceptibility alleles in chronic lymphocytic leukemia (CLL). Nevertheless, these studies scarcely study regions that are implicated in non-coding molecules such as microRNAs (miRNAs). Abnormalities in miRNAs, as altered expression patterns and mutations, have been described in CLL, suggesting their implication in the development of the disease. Genetic variations in miRNAs can affect levels of miRNA expression if present in pre-miRNAs and in miRNA biogenesis genes or alter miRNA function if present in both target mRNA and miRNA sequences. Therefore, the present study aimed to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA processing genes contribute to predisposition for CLL. A total of 91 SNPs in 107 CLL patients and 350 cancer-free controls were successfully analyzed using TaqMan Open Array technology. We found nine statistically significant associations with CLL risk after FDR correction, seven in miRNA processing genes (rs3805500 and rs6877842 in DROSHA, rs1057035 in DICER1, rs17676986 in SND1, rs9611280 in TNRC6B, rs784567 in TRBP and rs11866002 in CNOT1) and two in pre-miRNAs (rs11614913 in miR196a2 and rs2114358 in miR1206). These findings suggest that polymorphisms in genes involved in miRNAs biogenesis pathway as well as in pre-miRNAs contribute to the risk of CLL. Large-scale studies are needed to validate the current findings.

SummaryLosses in 13q as a sole abnormality confer a good prognosis in chronic lymphocytic leukaemia (CLL). Nevertheless, its heterogeneity has been demonstrated and the clinical significance of biallelic 13q deletions remains controversial. We compared the clinico-biological characteristics of a series of 627 patients harbouring isolated 13q deletions by fluorescence in situ hybridization (FISH), either monoallelic (13q 9 1), biallelic (13q 9 2), or the coexistence of both clones (13qM). The most frequent 13q deletion was 13q 9 1 (82Á1%), while 13q 9 2 and 13qM represented 8Á6% and 9Á3% of patients respectively. The median percentage of altered nuclei significantly differed across groups: 55%, 72Á5% and 80% in 13q 9 1, 13q 9 2 and 13qM (P < 0Á001). However, no significant differences in the clinical outcome among 13q groups were found. From 84 patients with sequential FISH studies, eight patients lost the remaining allele of 13q whereas none of them changed from 13q 9 2 to the 13q 9 1 group. The percentage of abnormal cells detected by FISH had a significant impact on the five-year cumulative incidence of treatment and the overall survival, 90% being the highest predictive power cut-off. In conclusion, loss of the remaining 13q allele is not enough to entail a worse prognosis in CLL. The presence of isolated 13q deletion can be risk-stratified according to the percentage of altered cells.