One of the most severe complications after successful cancer therapy is the development of therapy-related myeloid neoplasms (t-MN). Constitutional genetic variation is likely to impact on t-MN risk. We aimed to evaluate if polymorphisms in the p53 pathway can be useful for predicting t-MN susceptibility. First, an association study revealed that the Pro variant of the TP53 Arg72Pro polymorphism and the G allele of the MDM2 SNP309 were associated with t-MN risk. The Arg variant of TP53 is more efficient at inducing apoptosis, whereas the Pro variant is a more potent inductor of cell cycle arrest and DNA repair. As regards MDM2 SNP309, the G allele is associated with attenuation of the p53 apoptotic response. Second, to evaluate the biological effect of the TP53 polymorphism, we established Jurkat isogenic cell lines expressing p53Arg or p53Pro. Jurkat p53Arg cells presented higher DNA damage and higher apoptotic potential than p53Pro cells, after treatment with chemotherapy agents. Only p53Pro cells presented t(15;17) translocation and del(5q). We suggest that failure to repair DNA lesions in p53Arg cells would lead them to apoptosis, whereas some p53Pro cells, prone to cell cycle arrest and DNA repair, could undergo misrepair, generating chromosomal abnormalities typical of t-MN.

European Research Initiative on CLL (ERIC). (2015)Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia, 29, 329-336. Del Giudice, I., Marinelli, M., Wang, J., Bonina, S., Messina, M., Chiaretti, S., Ilari, C., Cafforio, L., Raponi, S., Mauro, F.R., Di Maio, V., De Propris, M.S., Nanni, M., Ciardullo, C., Rossi, D., Gaidano, G., Guarini, A., Rabadan, R. & Fo a, R.(2016) Inter-and intra-patient clonal and subclonal heterogeneity of chronic lymphocytic leukaemia: evidences from circulating and lymph nodal compartments. British Journal of Haematology, 172, 371-383. Diop, F., Moia, R., Favini, C., Spaccarotella, E., De Paoli, L., Bruscaggin, A., Spina, V., Cerri, M., Deambrogi, C., Kodipad, A.A., Favini, S., Sagiraju, S., Jabangwe, C., Mauro, F.R., Del Giudice, I., Forconi, F., Cortelezzi, A., Zaja, F., Visco, C., Chiarenza, A., Rigolin, G. Impact of polymorphisms in apoptosis-related genes on the outcome of childhood acute lymphoblastic leukaemiaDespite intensification of therapy, 20% of children with acute lymphoblastic leukaemia (ALL) relapse (Ceppi et al, 2015).The different response to chemotherapy may be partially explained by inherited genetic variants, e.g. single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). However, clinically useful genetic predictors of ALL treatment response are yet to be identified. We investigated the association between polymorphisms in genes encoding drug-metabolizing enzymes or apoptosis-related proteins and early-treatment response, minimal residual disease (MRD), relapse, overall survival (OS) and event-free survival (EFS) in 173 Caucasian children with ALL. Patients were genotyped for CNVs of CYP2D6, GSTT1, GSTM1, UGT2B17 and SULT1A1, and for SNPs of CYP2D6, SULT1A1 and TP53 (see Supporting Information). This is the first report to seek an association between the exact number of copies (0, 1, 2, ≥3) in selected candidate genes and ALL prognosis, and the first study to analyse the TP53 Arg72Pro polymorphism as a possible predictor of treatment response in childhood ALL.As expected for the Caucasian population, around 50% of children with ALL presented a GSTM1 null genotype, whereas most patients had one copy of GSTT1 and UGT2B17, and two copies of CYP2D6 and SULT1A1. The G allele was predominant in CYP2D6 and SULT1A1 SNPs, and C allele was predominant in TP53 SNP (Tables SI and SII).The association analysis between genotypes and earlytreatment response, MRD or relapse revealed no gene dose or SNP effect with any of the genetic models tested. However, interestingly, patients with 1, 2 or ≥ 3 copies of GSTM1 had worse outcome than patients with GSTM1 null genotype, both when genotypes were analysed separately (OS P = 0Á013, Figure S1A; EFS P = 0Á047, Figure S1B) and when all non-null genotypes were grouped together (OS P = 0Á002, Fig 1A; EFS P = 0Á005, Figure S1C). Differences between null and non-null individuals were confirmed in multivariate analysis for OS (hazard ratio [HR] = 16Á51; 95% confidence interval [CI] 2Á13-128Á18; P = 0Á007...

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ResumenEl Plasmocitoma-like es una entidad poco frecuente englobada dentro de los trastornos linfoproliferativos postransplante (TLPT). La inmunosupesión y la infección con virus de Epstein-Barr (VEB) juegan un papel primordial en su desarrollo. Su diagnóstico preoperatorio es difícil si no se aplican estudios inmunohistoquímicos sobre las biopsias, y el tratamiento adecuado debe ser quirúrgico y/o radioterápico, asociado a la reducción de la dosis de inmunosupresores. El seguimiento de estos enfermos debe ser estrecho ya que puede ocurrir la recurrencia del tumor, así como la aparición de rechazo del trasplante por la disminución de los inmunosupresores.Presentamos un paciente trasplantado cardíaco que desarrolló un TLPT tipo "plasmocitoma-like" en el estómago siete años después del trasplante, comentamos las teorías etiopatogénicas, los criterios diagnósticos y sus posibilidades de tratamiento. Palabras clave: Plasmocitoma-like. Trastorno linfoproliferativo postransplante (TLPT). Virus de Epstein-Barr (VEB). Inmunosupresión. Oncología, 2006; 29 (7):307-312

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