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Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.

El presente artículo analiza las relaciones entre activismo lésbico y arte político en Buenos Aires, Argentina, durante los primeros años de la década de 1990. Para ello se centra en el grupo Lesbianas en la Resistencia, que intervino durante 1995-1997 en la plaza pública más importante —por su significado tanto histórico-simbólico como político— de la ciudad de Buenos Aires: la Plaza de Mayo. A partir de la reconstrucción de la historia del grupo, mediante la memoria oral de sus integrantes, el ensayo busca trazar —desde una metodología feminista y queer— una cartografía de los elementos centrales de la acción del grupo: el cuerpo, la visibilidad y la construcción de un hacer colectivo con materiales “precarios o de desecho”. Esta investigación nos permitió recuperar una experiencia poco conocida en la historiografía local, indagar en los modos en que se articularon la militancia lésbica y el activismo artístico durante esos años de contexto neoliberal, y generar modos de recuperación de la memoria colectiva LGBTTT que sirven para pensar el presente.

Recurrent immunoglobulin heavy chain (IGH) translocations - t(14q32) - such as t(4;14) or t(11;14) are considered to be primary cytogenetic events which play an important role in the pathogenesis of clonal plasma cell (PC) disorders. However, previous cytogenetic studies in these diseases have mainly been done in whole bone marrow or CD138+ microbead-enriched PC; the latter technique has several pitfalls such as coexistence of CD138+ and CD138− aberrant PC or apoptotic loss of CD138.Overall, highly-purified aberrant PC (purity ≥98%) from 217 patients with either multiple myeloma (MM; n=155) or monoclonal gammopathy of undetermined significance (MGUS; n=62) were analyzed for the presence of different cytogenetic alterations such as del(13q14), del(17p13) and t(14q32) by multicolor interphase fluorescence in situ hybridization (iFISH). Purity of sorted PC populations was further confirmed by iFISH studies of residual normal - i.e. polyclonal - PC fractions in a subgroup of 10 exemplarily cases with clonal PC disorder. Additionally, analysis of IGH gene arrangements and complementarity determining region 3 (CDR3) sequencing was carried out in a subset of patients (n=9) and simultaneous application of iFISH and immunofluorescent protein staining (FICTION) was performed in selected cases to confirm the clonal relationship between different fractions of tumor PC from individual patients and specific cytogenetic findings.At diagnosis, 96% of all MM vs. 77% of MGUS cases (p<0.001) showed ≥1 cytogenetic alteration and/or hyperdiploidy. Interestingly, among cases with t(14q32), in 24% of MM vs. 62% of MGUS patients (p=0.02) aberrant PC with and without IGH translocation - e.g. t(4;14) or t(11;14) - coexisted in the same patient. Furthermore, longitudinal cytogenetic studies in a subset of MM patients at different stages of the disease showed that an aberrant PC subclone lacking a recurrent t(14q32) might even expand during disease evolution. PCR and sequencing studies confirmed the existence of only one unique CDR3 sequence - in the absence of an oligo-/polyclonal background - in all tested samples indicating clonal relationship of cytogenetically-defined aberrant PC subclones. These observations together with FICTION analyses performed in selected cases, led further to assume that our findings are not due to contaminating residual normal PC. Finally, MM and MGUS cases frequently showed different but related cytogenetic profiles when other cytogenetic alterations which were presumably sequentially acquired by the PC, such as deletions/gains of IGH, FGFR3, CCND1 and MAF, as well as the DNA ploidy status determined by multiparameter flow cytometry were additionally considered.Our findings using highly-purified aberrant PC suggest that also recurrent IGH translocations might evolve secondarily during disease evolution in a significant fraction of MGUS and MM cases, which raises the question about their precise role in the pathogenesis of clonal PC disorders. Our data further supports the existence of a high intratumoral cytogenetic heterogeneity in MM and MGUS, challenging individualized treatment approaches in these diseases.No relevant conflicts of interest to declare.

Abstract 3945