BACKGROUND: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed,

The prognosis of adult normal karyotype (NK) precursor B cell acute lymphoblastic leukemia (B-ALL) has not improved over the last decade mainly because separation into distinct molecular subsets has been lacking and no targeted treatments are available. We screened the genome of blasts from ten adult NK B-ALL patients for novel genomic alterations by array comparative genomic hybridization and verified our results with fluorescent in situ hybridization and gene expression profile using the same probes. The results demonstrate cryptic deletions of 9q34 involving SET, PKN3, NUP188, ABL1 and NUP214 in three of the samples. The smallest deletion resulted in the likely juxtaposition of the SET and NUP214 genes. This aberration has not been described before in adult NK B-ALL. Larger number of samples is warranted to determine the prognostic significance of this cryptic deletion.

unresponsiveness could explain the absence of cell death effects after STAT6 siRNA transfection and could be due to the activation of other transcription factors, such as nuclear factorkB, known to control BCL-XL expression.To test whether the phosphorylation status of STAT6 and its nuclear translocation coincides with the expression of BCL-XL protein in vivo, we studied their expression in a series of 28 tumor samples, collected between 1988 and 1998 in the Institute of Pathology of Ulm. Twenty-six out of 28 PMBL cases exhibited nuclear staining for P-STAT6 in more than 40% of the neoplastic cells and 25 out of 28 PMBL cases exhibited cytoplasmic staining for BCL-XL in more than 50% of the neoplastic cells. There was a clear correlation between nuclear P-STAT6 accumulation and BCL-XL expression as 25 out of 28 cases (89%) showed staining for both ( Figure 3e, A and C), whereas 2 out of 28 cases (7%) were negative for both ( Figure 3e, B and D). Actually, there was just one single case with a high percentage of P-STAT6 positive lymphoma nuclei and a very low percentage of BCL-XL-positivity within the lymphoma cell compartment. This might be due to the absence of transcriptional activators required to activate BCL-XL transcription in association with STAT6, such as nuclear factor-kB or Ets transcription factors. According to the linear correlation analysis, we found a Pearson correlation coefficient of r ¼ 0.39 (Po0.05) between the percentage of the cells immunoreactive for BCL-XL and the percentage of the cells immunoreactive for P-STAT6. In summary, these data strongly suggest that STAT6 upregulates BCL-XL expression not only in MedB-1 cells but also in PMBL tumors.Altogether, our results provide evidence that SOCS-1 gene defects strongly contribute to constitutive STAT6 activation and promote cell survival in PMBL cell lines. STAT6 regulates cell proliferation and survival and BCL-XL expression in MedB-1 cells. Its association with BCL-XL expression in primary PMBL cases suggests that the deregulation of the SOCS1/STAT6 pathway plays a critical role in PMBL pathogenesis. AcknowledgementsWe thank Adeline Henry for help in flow cytometry. We are thankful to William Hempel for careful reading and editing the paper.O Ritz 1,7 , C Guiter 2,3,4,7 These authors contributed equally to this study.

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