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Introduction It was recently proposed that the molecular breast tumor subtypes are differently distributed in the elderly breast cancer patients, and also lack prognostic value. Given the limited number of elderly patients in previous studies, the aim of this study was to determine the prognostic effect of the molecular intrinsic subtypes in a large older breast cancer population. Material and method Older breast cancer patients with invasive, non-metastatic breast cancer with tumor material available for immunohistochemical determination of Ki67, EGFR, CK5/6 and HER-2 were included. ER and PR expression was retrieved from the pathology report. Molecular subtypes were: Luminal A, Luminal B, ERBB2, Basal-like and Unclassified. Primary endpoint was Relapse Free Period (RFP), taking into account the competing risk of mortality, and adjusted for the most important patient, tumor and treatment characteristics. Secondary endpoint was Relative Survival (RS). Results Overall, 1362 patients were included. Patients with a Luminal A subtype had the lowest risk of recurrence (11% at 5 yrs). Patients with a Basal (24% at 5yrs) or ERBB2 (34% at 5yrs) molecular breast tumor subtype had the highest risk of recurrence. The ERBB2 subtype had the worst prognosis in terms of RFP (SHR 2.07, 95% CI 1.35–3.20; p = 0.001). The worst RS was again observed for the ERBB2 subtype (48% at 10 yrs). In multivariable analyses, the relative excess risk of death for all molecular subtypes was significantly worse compared to the Luminal A subtype. Conclusion Molecular intrinsic breast tumor subtypes have significant prognostic value in the elderly population, even after taking competing mortality into account. [ABSTRACT FROM AUTHOR]

Outcomes in childhood T-cell acute lymphoblastic leukaemia (T-ALL) are steadily improving due to intensive therapy. Between 1989 and 2008, 599 children with newly diagnosed T-ALL were enrolled in two successive European Organization for Research and Treatment of Cancer - Children's Leukaemia Group trials (58881 and 58951), both based on the Berlin-Frankfurt-Munster protocol and without cranial irradiation. In the latter trial induction chemotherapy was intensified. The most important randomizations were Medac Escherichia coli asparaginase versus Erwinia asparaginase in trial 58881, and dexamethasone (6 mg/m 2 /day) versus prednisolone (60 mg/m 2 /day) and prolonged versus conventional asparaginase duration in trial 58951. 8-year event-free survival (EFS) increased from 65·1% to 74·0% in trial 58951. Improvement was most profound for patients with white blood cell (WBC) counts <100 × 10 9 /l and "good responders" to prephase. Medac E. coli asparaginase was associated with longer EFS [hazard ratio (HR) 0·54, P = 0·0015] and overall survival (HR 0·51, P = 0·0018). Induction therapy with dexamethasone did not improve EFS compared to prednisolone. Remarkably, intensification of central nervous system (CNS)-directed therapy in trial 58951 resulted in fewer bone marrow relapses, while the incidence of CNS relapses remained low. In summary, we showed that adequate asparaginase therapy, intensified induction treatment and intensification of CNS-directed chemotherapy can result in an improvement of outcome in T-ALL patients with good prephase response and initial WBC counts <100 × 10 9 /l, representing approximately 50% of T-ALL patients., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Chromosomal rearrangements involving the MECOM (MDS1 and EVI1 complex) locus are recurrent genetic events in myeloid leukaemia and are associated with poor prognosis. In this study, we assessed the role of MECOM locus protein EVI1 in the transcriptional regulation of microRNAs (miRNAs) involved in the leukaemic phenotype. For this, we profiled expression of 366 miRNAs in 38 MECOM-rearranged patient samples, normal bone marrow controls and MECOM (EVI1) knock down/re-expression models. Cross-comparison of these miRNA expression profiling data showed that MECOM rearranged leukaemias are characterized by down regulation of MIR449A. Reconstitution of MIR449A expression in MECOM-rearranged cell line models induced apoptosis resulting in a strong decrease in cell viability. These effects might be mediated in part by MIR449A regulation of NOTCH1 and BCL2, which are shown here to be bona fide MIR449A targets. Finally, we confirmed that MIR449A repression is mediated through direct promoter occupation of the EVI1 transcriptional repressor. In conclusion, this study reveals MIR449A as a crucial direct target of the MECOM locus protein EVI1 involved in the pathogenesis of MECOM-rearranged leukaemias and unravels NOTCH1 and BCL2 as important novel targets of MIR449A. This EVI1-MIR449A-NOTCH1/BCL2 regulatory axis might open new possibilities for the development of therapeutic strategies in this poor prognostic leukaemia subgroup., (© 2011 Blackwell Publishing Ltd.)

Classical Hodgkin lymphoma (cHL) is characterized by the presence of malignant Hodgkin and Reed Sternberg (HRS) cells. The scarcity of tumour cells in lymphoma biopsies has hampered genetic analyses of HRS cells, including microRNA (miRNA) expression profiling. We determined the expression of 360 miRNAs in microdissected HRS cells from nine cHL patients. These miRNA profiles were compared to those from four cHL cell lines and CD77+ B-cells, yielding a distinct cHL signature of 12 over- and three underexpressed miRNAs. Our data suggest that miRNAs are implicated in the pathogenesis of Hodgkin lymphoma and prompt further investigations concerning their role in cHL.

Paediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco- and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.