CLLU1 expression has prognostic value in chronic lymphocytic leukemia after first-line therapy in younger patients and in those with mutated IGHV genes.

CLLU1, located at chromosome 12q22, encodes a transcript specific to chronic lymphocytic leukemia and has potential prognostic value. We assessed the value of CLLU1 expression in the LRF CLL4 randomized trial. Samples from 515 patients with chronic lymphocytic leukemia were collected immediately before the start of treatment. After RNA extraction and cDNA synthesis, CLLU1 expression was assessed by quantitative polymerase chain reaction. In total, 247 and 268 samples were identified as having low and high CLLU1 expression, respectively. The median follow-up was 88 months. High CLLU1 expression was significantly correlated with unmutated IGHV genes, ZAP-70 and CD38 positivity, and absence of 13q deletion (all r>0.2, P

Mutational Status of the TP53 Gene As a Predictor of Response and Survival in Patients With Chronic Lymphocytic Leukemia: Results From the LRF CLL4 Trial

PurposeTP53 mutations have been described in chronic lymphocytic leukemia (CLL) and have been associated with poor prognosis in retrospective studies. We aimed to address the frequency and prognostic value of TP53 abnormalities in patients with CLL in the context of a prospective randomized trial.Patients and MethodsWe analyzed 529 CLL samples from the LRF CLL4 (Leukaemia Research Foundation Chronic Lymphocytic Leukemia 4) trial (chlorambucil v fludarabine with or without cyclophosphamide) at the time of random assignment for mutations in the TP53 gene. TP53 mutation status was correlated with response and survival data.ResultsMutations of TP53 were found in 40 patients (7.6%), including 25 (76%) of 33 with 17p deletion and 13 (3%) of 487 without that deletion. There was no significant correlation between TP53 mutations and age, stage, IGHV gene mutations, CD38 and ZAP-70 expression, or any other chromosomal abnormality other than 17p deletion, in which concordance was high (96%). TP53 mutations were significantly associated with poorer overall response rates (27% v 83%; P <.001) and shorter progression-free survival (PFS) and overall survival (OS; 5-year PFS: 5% v 17%; 5-year OS: 20% v 59%; P <.001 for both). Multivariate analysis that included baseline clinical variables, treatment, and known adverse genetic factors confirmed that TP53 mutations have added prognostic value.ConclusionTP53 mutations are associated with impaired response and shorter survival in patients with CLL. Analysis of TP53 mutations should be performed in patients with CLL who have progressive disease before starting first-line treatment, and those with mutations should be selected for novel experimental therapies. J Clin Oncol 29: 2223-2229. (C) 2011 by American Society of Clinical Oncology

Ochrona prawna zdolności do życia zarodka w ustawie o leczeniu niepłodności z uwzględnieniem dorobku konstytucyjnego

Od wielu lat niepłodność pozostaje przedmiotem dyskusji medycznych, jak i prawnych. Choroba ta jest problemem o szerokim zasięgu społecznym, dotyka bowiem coraz większej liczby osób starających się o potomstwo. Uznanie niepłodności za chorobę a procedurę zapłodnienia pozaustrojowego za jedną z metod jej leczenia ma swoje doniosłe konsekwencje prawne. Z jednej strony mamy do czynienia z konstytucyjną ochroną prawa do ochrony zdrowia niepłodnej pary, ale z drugiej strony jawi się kolejna konstytucyjna wartość wymagająca ochrony – życie mającego się urodzić dziecka. Ustawodawca dostrzegł potrzebę uregulowania metod leczenia niepłodności, czego konsekwencją jest ustawa z dnia 25 czerwca 2015 r. o leczeniu niepłodności. Tematem artykułu jest ocena, na ile i czy w ogóle ustawodawca w przedmiotowej ustawie zapewnia ochronę prawną zdolności do życia zarodka.