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Prostate adenocarcinoma (CaP) patients are classified into low-, intermediate-, and high-risk groups that reflect relative survival categories. While there are accepted treatment regimens for low- and high-risk patients, intermediate-risk patients pose a clinical dilemma, as treatment outcomes are highly variable for these individuals. A better understanding of the factors that regulate the progression of CaP is required to delineate risk. For example, aberrant activation of the Hedgehog (Hh) pathway is implicated in CaP progression. Here, we identify the serine protease inhibitor protease nexin 1 (PN1) as a negative regulator of Hh signaling in prostate. Using human CaP cell lines and a mouse xenograft model of CaP, we demonstrate that PN1 regulates Hh signaling by decreasing protein levels of the Hh ligand Sonic (SHH) and its downstream effectors. Further-more, we show that SHH expression enhanced tumor growth while overexpression of PN1 inhibited tumor growth and angiogenesis in mice. Finally, using comparative genome hybridization, we found that genetic alterations in Hh pathway genes correlated with worse clinical outcomes in intermediate-risk CaP patients, indicating the importance of this pathway in CaP., Introduction Prostate adenocarcinoma (CaP) is the second leading cause of male cancer death in the Western world (1). Various risk groups (low, intermediate, high, and metastatic) that reflect relative survival [...]

SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL), however its prognostic implication remains controversial. To investigate the clinical characteristics and outcome of this subtype in Chinese population, we systemically reviewed 62 patients with newly diagnosed T-ALL, including 15 patients with SIL-TAL1 rearrangement. We found that SIL-TAL1+ T-ALL was characterized by higher white blood cell count (P = 0.029) at diagnosis, predominant cortical T-ALL immunophenotype (P = 0.028) of the leukemic blasts, and a higher prevalence of tumor lysis syndrome (TLS, P<0.001) and disseminated intravascular coagulation (DIC, P<0.001), which led to a higher early mortality (P = 0.011). Compared with SIL-TAL1− patients, SIL-TAL1+ patients had shorter relapse free survival (P = 0.007) and overall survival (P = 0.002). Our NOD/SCID xenotransplantation model also demonstrated that SIL-TAL1+ mice models had earlier disease onset, higher leukemia cell load in peripheral blood and shorter overall survival (P<0.001). Moreover, the SIL-TAL1+ mice models exerted a tendency of TLS/DIC and seemed vulnerable towards chemotherapy, which further simulated our clinical settings. These data demonstrate that SIL-TAL1 rearrangement identifies a distinct subtype with inferior outcome which could allow for individual therapeutic stratification for T-ALL patients. [ABSTRACT FROM AUTHOR]

Acute Promyelocytic Leukemia (APL) is one of the most curable leukemia which shows great sensitivity to all-trans retinoic acid (ATRA) although a small number of the patients present poor prognosis and short survival. Isochromosome 17 in APL which usually bears an additional copy of RARA/PML fusion gene is considered to be a negative factor on its prognosis. Cryptic t(15;17) on i(17q) leads to an extra copy of PML/RARA rather than RARA/PML which may confer a worse prognosis. We describe here a rare APL case with complex chromosomal abnormality including isochromosome 17 bearing cryptic t(15;17) showing poor outcome. The patient lacks a classic t(15;17) and fluorescence in situ hybridization (FISH) presents 2 PML/RARA fusion signals on both long arms of the isochromosome. The patient also acquired a secondary mutation at relapse when the initial karyotype was already a complex karyotype involving chromosome 13, 17 and 22 at the same time. The poor response of this patient to traditional chemotherapy like ATRA and novel therapy like arsenic trioxide (ATO) suggests that early auto-hematological stem cell transplantation may be the choice of APL with isochromosome 17 especially with cryptic t(15;17) on i(17q). We are the first to show a clear history and evidence of FISH of these kind of cases. A small summary of cases with cryptic t(15;17) on isochromosome 17 is also made.

Ikaros6 was specifically associated with clinical and genetic features of acute lymphoblastic leukemia (ALL) and could be used for prediction of inferior survival. The present study aimed to further investigate the correlation between Ikaros6 and other prognostic factors, and to explore the novel prognosis prediction function by combining Ikaros6 and other factors in Chinese adult B-ALL. We examined the expression of Ikaros6 in 108 patients by reverse transcription polymerase chain reaction and confirmed the results by sequencing, gene scanning and real-time PCR. Ikaros6 was associated with BCR-ABL1 (P=0.010) and myeloid-associated antigens (P=0.009), but had an independent negative impact on survival. In multivariable Cox analysis, Ikaros6 was an independent prognostic marker for overall survival (P=0.013, HR=2.140), event-free survival (P=0.016, HR=1.972) and relapse-free survival (P=0.002, HR=3.636). This study indicated closed relation between BCR-ABL1, myeloid-associated antigens and Ikaros6.These three risk factors played an important role in evaluation of prognosis in Chinese adult B-ALL. Furthermore, Ikaros6 is more beneficial for the disease recurrence prediction.