Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent ß-thalassemia intermedia.

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) ß-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11 years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis. Three groups of patients were identified: homozygous ß+ (N = 18), heterozygous ß0ß+ (N = 22), and homozygous ß0 (N = 20). The groups were homogeneous for sex, age, splenectomy, hematochemical parameters, chelation therapy, and iron levels. The homozygous ß° genotype was associated with significantly higher biventricular end-diastolic and end-systolic volume indexes and bi-atrial area indexes. No difference was detected in biventricular ejection fractions or myocardial fibrosis. Extramedullary hematopoiesis and leg ulcers were significantly more frequent in the homozygous ß° group compared to the homozygous ß+ group. No association was detected between genotype and liver cirrhosis, hypogonadism, hypothyroidism, osteoporosis, heart failure, arrhythmias, and pulmonary hypertension. Heart remodelling related to a high cardiac output state cardiomyopathy, extramedullary hematopoiesis, and leg ulcers were more pronounced in patients with the homozygous ß° genotype compared to the other genotypes analyzed. The knowledge of the genotype can assist in the clinical management of NTD ß-TI patients.

Zeb1 maintains long-term adult hematopoietic stem cell function and extramedullary hematopoiesis.

Emerging evidence implicates the epithelial-mesenchymal transition transcription factor Zeb1 as a critical regulator of hematopoietic stem cell (HSC) differentiation. Whether Zeb1 regulates long-term maintenance of HSC function remains an open question. Using an inducible Mx-1-Cre mouse model that deletes conditional Zeb1 alleles in the adult hematopoietic system, we found that mice engineered to be deficient in Zeb1 for 32 weeks displayed expanded immunophenotypically defined adult HSCs and multipotent progenitors associated with increased abundance of lineage-biased/balanced HSC subsets and augmented cell survival characteristics. During hematopoietic differentiation, persistent Zeb1 loss increased B cells in the bone marrow and spleen and decreased monocyte generation in the peripheral blood. In competitive transplantation experiments, we found that HSCs from adult mice with long-term Zeb1 deletion displayed a cell autonomous defect in multilineage differentiation capacity. Long-term Zeb1 loss perturbed extramedullary hematopoiesis characterized by increased splenic weight and a paradoxical reduction in splenic cellularity that was accompanied by HSC exhaustion, lineage-specific defects, and an accumulation of aberrant, preleukemic like c-kit+CD16/32+ progenitors. Loss of Zeb1 for up to 42 weeks can lead to progressive splenomegaly and an accumulation of Gr-1+Mac-1+ cells, further supporting the notion that long-term expression of Zeb1 suppresses preleukemic activity. Thus, sustained Zeb1 deletion disrupts HSC functionality in vivo and impairs regulation of extramedullary hematopoiesis with potential implications for tumor suppressor functions of Zeb1 in myeloid neoplasms.

Angiomiolipoma epitelioide hepático: correlación clínico-patológica en una serie de 4 casos / Epithelioid angiomyolipoma of the liver: clinicopathological correlation in a series of 4 cases

El angiomiolipoma hepático es una neoplasia rara que puede llegar a ser difícil de diagnosticar en casos de biopsia ecoguiada. Hemos estudiado 4 casos de pacientes de sexo femenino, con una media de edad de 51 años. Ninguno de los pacientes se ha presentado con síntomas abdominales específicos, ni otras masas tumorales detectadas incidentalmente. Uno de ellos tenía antecedentes personales relevantes: carcinoma de células renales. Este mismo paciente fue diagnosticado de un angiomiolipoma renal contralateral. Ninguno de los pacientes ha mostrado evidencia de padecer esclerosis tuberosa. Tres de los tumores han sido diagnosticados por biopsia y en sólo uno de los pacientes se ha decidido la extirpación quirúrgica completa del tumor. En ninguno de los pacientes se ha observado evidencia de recidiva de la enfermedad o aumento del tamaño tumoral durante un periodo medio de 45 meses. Histológicamente los tumores se han subclasificado en angiomiolipomas epitelioides. En el 50% de los casos se ha observado hematopoyesis extramedular. La primera impresión diagnóstica mediante métodos de imagen incluía: hiperplasia nodular focal, adenoma hepático, carcinoma hepatocelular y metástasis. Mediante técnicas de inmunohistoquímica se ha demostrado que todos los tumores expresaban marcadores melanocíticos (HMB45 y Melan A) y marcadores de células musculares lisas (actina de músculo liso). El diagnóstico de estos tumores está aumentando debido a los programas de detección precoz de carcinoma hepatocelular en pacientes con cirrosis. Hay que tener en cuenta su amplio espectro de diversidad morfológica para evitar el diagnóstico incorrecto de una neoplasia maligna (AU)

Hepatic angiomyolipoma is a rare neoplasm that can be difficult to diagnose in cases of ecoguide biopsy. We studied 4 cases of female patients with a mean age of 51 years. None of the patients presented specific abdominal symptoms, or other tumour masses detected by chance. One of them had relevant personal history: Renal cell carcinoma. This same patient was diagnosed with a contralateral renal angiomyolipoma. None of the patients showed evidence of tuberous sclerosis. Three tumours have been diagnosed by biopsy and only in one patient was decided to completely remove the tumour surgically. None of the patients had evidence of recurrence of disease or an increase in tumour size over an average period of 45 months. Histologically, the tumours have been sub classified into angiomyolipomas epithelioid. In 50% of the cases, extramedullary haematopoiesis was observed. The first diagnostic impression using imaging methods included: Focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma and metastasis. By immunohistochemistry, it has been demonstrated that all tumours expressing melanocytic markers (HMB45 and Melan A) and markers of smooth muscle cells (smooth muscle actin). The diagnosis of these tumours is increasing due to programmes for early detection of hepatocellular carcinoma in patients with liver cirrhosis. It must be taken into account their broad spectrum of morphological diversity to avoid incorrect diagnosis of a malignant neoplasm (AU)