CCAAT/enhancer-binding protein alpha (CEBPA) gene haploinsufficiency does not alter hematopoiesis or induce leukemia in Lck-CALM/AF10 transgenic mice

Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.

Mycobacterium marinum: reporte de un caso / Mycobacterium marinum: a case report

El Mycobacterium marinum es un tipo de micobacteria no tuberculosa (NTM). La infección por esta bacteria es frecuente en peces de agua dulce o salada y muy raramente, suele causar infecciones en la población humana. Presentamos el caso de un paciente varón de 60 años, que consulta por placa ulcerosa en dorso de mano izquierda. El estudio histopatológico de biopsia informa: hiperplasia epitelial con un denso infiltrado en dermis y escasos granulomas con células gigantes. Se solicitan distintas pruebas, siendo únicamente positiva el PCR para Mycobacterium marinum, por lo que se procede a instaurar regimen antimicrobiano con evolución favorable. El contagio por esta bacteria, se produce por inoculación directa del microorganismo, a través de heridas o erosiones cutáneas o por mordeduras de peces contaminados. Las formas de presentación clínica varían, siendo la más común la presencia de pápulas o nódulos solitarios en dedos o manos. También se puede manifestar en forma de linfangitis proximal o esporotricoide, extensión a órganos profundos y patrón esporotricoide facial. El diagnóstico requiere un alto índice de sospecha, debido a que la frecuencia de esta afección es muy baja, siendo de 0.04 a 0.27 por cada 100.000 habitantes. La biopsia de tejido proporciona el diagnóstico en solo la mitad de los casos. El cultivo confirma el diagnóstico, pero se reportan como positivos en 70 a 80% de los casos. Técnicas de amplificación de ácidos nucleicos, como la reacción en cadena polimerasa (PCR) son otros métodos para el diagnóstico, su mayor ventaja es la rapidez de sus resultados en comparación con el cultivo. Existen muchas modalidades terapéuticas: el tratamiento tópico, la administración sistémica de antimicrobianos, la cirugía, la termoterapia local y la terapia combinada. Sin embargo, los pacientes infectados con M. marinum por lo común, son tratados con antimicrobianos en monoterapia o combinados.

Introduction: Mycobacterium marinum is a type of non-tuberculous mycobacterium (NTM). Infection by this bacterium is frequent in freshwater or saltwater fish and very rarely causes infection in human population. Case report: we present the case of a 60-year-old male patient, who consulted for an ulcerative plaque on the back of his left hand. The histopathological study of biopsy reports: epithelial hyperplasia with a dense infiltrate in dermis and few granulomas with giant cells. Different tests were requested, PCR the only one positive for Mycobacterium marinum, which is why we proceeded to establish an antimicrobial regimen with favorable evolution. Discussion: infection by this bacterium is produced by direct inoculation of the microorganism through wounds or skin erosions or by contaminated fish bites. The forms of clinical presentation vary, being the most common the presence of solitary papules or nodules on fingers or hands. It can also manifest in the form of proximal or sporotrichoid lymphangitis, extension to deep organs, and facial sporotrichoid pattern. Diagnosis requires high index of suspicion, since the frequency of this condition is very low, from 0.04 to 0.27 per 100.000 habitants. Tissue biopsy provides the diagnosis in only half of the cases. Culture confirms the diagnosis, but they are reported as positive in 70 to 80% of cases. Nucleic acid amplification techniques, such as polymerase chain reaction (PCR) are other methods for diagnosis; its greatest advantage is the speed of its results compared to culture. There are many therapeutic modalities: topical treatment, systemic administration of antimicrobials, surgery, local thermotherapy and combination therapy. However, patients infected with M. marinum are usually treated with antimicrobials alone or in combination.