PubMed Health⌕ Search

Biomedical subjects

Héctor Mayani

Publications and source records attributed to Héctor Mayani.

7 recordsLinked to original sources

Expression of ice, bcl-2, c-myc and p53 in different bone marrow cell populations from patients with diffuse large B-cell lymphoma.

We have previously reported functional alterations in vitro in the hematopoietic compartment of patients with diffuse large B-cell lymphoma (DLBCL). In the present study, we assessed the presence of molecular alterations in hematopoietic cells derived from DLBCL marrow. Accordingly, the expression of four genes (i.e. ice, bcl-2, c-myc and p53) was assessed both, at the mRNA and protein levels, in three cell populations: (i) population I, consisting of morphologically recognizable precursor and mature cells; (ii) population II, enriched for CD34+ Lineage-negative (Lin-) cells; and (iii) population III, enriched for CD34+ CD38- Lin- cells. By using a multiplex reverse transcriptase-polymerase chain reaction system, we observed reduced expression of bcl-2 in population I, and c-myc in populations I and II from lymphoma marrow compared to their normal counterparts. On the other hand, expression of ice and p53 was not significantly different when comparing normal and DLBCL samples. At the protein level, all four molecules were expressed in a higher proportion of samples from DLBCL patients than in marrow samples from normal subjects. Interestingly, these proteins were expressed predominantly in primitive cells (population III), whereas the proportion of positive samples was reduced in population II, and even more in population I. Taken together, our results indicate that, in DLBCL, molecular alterations are present in hematopoietic cells from bone marrow, including morphologically recognizable precursor and mature cells, as well as primitive hematopoietic progenitors (CD34+ cells). To date, the physiological implications of these alterations are still unclear, and further studies should be undertaken to address this issue.

Adolescent↗

Biology of human hematopoietic stem and progenitor cells present in circulation.

Circulating hematopoietic stem and progenitor cells play important roles in the physiology and homeostasis of the hematopoietic system. The frequency of these cells varies throughout development, being more abundant during gestation. In the adult, the numbers of such cells are extremely low; however, they can be increased by intravenous administration of chemotherapy and/or recombinant cytokines to individuals. This mechanism--known as mobilization--involves the disruption of the interactions between primitive hematopoietic cells and microenvironment elements (stromal cells and extracellular matrix molecules), which are mediated by a group of molecules known as cell adhesion molecules. During the last two decades, circulating cells of newborns (those present in umbilical cord blood) and adults (mobilized peripheral blood) have gained relevance not only because of their biology, but also because of their clinical application. Indeed, at present the number of mobilized peripheral blood-derived hematopoietic cell transplants performed worldwide is clearly superior to the number of bone marrow transplants being done annually. On the other hand, the number of cord blood transplants has significantly increased during the last few years, and cord blood banking has expanded in a significant manner over the last decade. Circulating stem and progenitor cells are being manipulated ex vivo, both in cellular and molecular terms, and the clinical use of these manipulated cells is just beginning. Undoubtedly, hematopoietic cells present in circulation will play a key role in the development of both gene and cellular therapies for a variety of diseases.

Animals↗

In vitro proliferation, expansion, and differentiation of a CD34+ cell-enriched hematopoietic cell population from human umbilical cord blood in response to recombinant cytokines.

BACKGROUND: The conditions and mechanisms that control the in vitro growth of hematopoietic stem/progenitor cells (contained within the population of CD34+ cells) are still not completely understood. METHODS: By using an immunomagnetic system, we have enriched for umbilical cord blood (UCB)-derived CD34+ cells (55% of total cells recovered vs. 0.8% of total cells prior to the enrichment procedure) and analyzed their in vitro growth (proliferation, expansion, and differentiation) in a liquid culture system in the absence or presence of different recombinant cytokine combinations. RESULTS: When the selected cells were cultured in the absence of recombinant cytokines, no proliferation or expansion was observed. In the presence of steel factor (SF) and interleukin-6 (IL-6), total cell number was increased nearly fourfold; however, no progenitor cell expansion took place. When cultures were supplemented with SF and IL-6 together with IL-3 and erythropoietin (EPO), a rapid proliferation of the CD34+ -enriched cell population was observed with a selective stimulation of erythropoiesis. However, this stimulation was only transient, suggesting that there was a rapid exhaustion of erythroid progenitor cells within the first 10 days. Significantly higher levels of proliferation and expansion of progenitor cells were observed in the presence of SF, IL-6, GM-CSF, and G-CSF with preferential stimulation of myelopoiesis. Interestingly, such stimulation of myelopoiesis was sustained for the entire culture period (>30 days). The highest levels of proliferation and expansion were observed in the presence of all six cytokines. Under these conditions, erythropoiesis was also sustained only transiently (10 days), whereas myelopoiesis was sustained for >30 days. CONCLUSIONS: This study indicates that significant proliferation and expansion of hematopoietic progenitors can be achieved in vitro when culturing a cell population in which CD34+ cells comprise only >50% of the total cells. Our results also suggest that myeloid progenitors (those responding to GM-CSF and G-CSF) possess higher expansion potentials in vitro than their erythroid counterparts. The methods described here for the enrichment and culture of CD34+ cells may be relevant in the development of protocols for the ex vivo proliferation and expansion of hematopoietic progenitors for transplantation.

Antigens, CD34↗

A glance into somatic stem cell biology: basic principles, new concepts, and clinical relevance.

Somatic stem cells are undifferentiated cells with a high capacity for self-renewal that can give rise to one or more specialized cell types with specific functions in the body. Profound characterization of these cells has been difficult due to the fact that their frequency in different tissues of the body is extremely low; furthermore, their identification is not based on their morphology but on immunophenotypic and functional assays. Nevertheless, significant advances in the study of these cells at both cellular and molecular levels have been achieved during the last decade. The majority of what we know concerning somatic stem cell biology has come from work on hematopoietic stem cells. More recently, however, there has been a great amount of information on neural and epithelial stem cells. The importance of stem cell research has gone beyond basic biology and is currently contributing to the development of new medical approaches for treatment of hematologic, neurologic, autoimmune, and metabolic disorders (cellular therapy).

Animals↗

[New concepts in the biology of acute myeloid leukemia].

During the last 20 years, several concepts regarding the biology of acute myeloid leukemia (AML) have changed in a profound manner. This has been mainly due to significant advances in the identification, purification and characterization of the primitive hematopoietic cells--including stem and progenitor cells--in which this disorder originates. In the present review article, we discuss some of these new concepts and their relevance in the treatment of AML.

Antigens, CD34↗

[Diffuse large cell lymphoma: new molecular approaches].

The term lymphoma comprises a group of neoplasias that develop within the lymphatic system and represent one of the most frequent types of cancer worldwide. During the last decade, significant advances on the molecular biology of lymphoma have been achieved, which have been important not only to understand the etiology of this disease, but also in the development of fast and accurate diagnostic and prognostic methods, which in turn, will allow us to develop appropriate treatments for individual patients. Current systems for the classification of lymphomas have also been influenced by new molecular tools, recently developed. The main goal of this article is to present a general view on the latest advances in the molecular biology of lymphoma. In order to do so, we have focused on Diffuse Large B-Cell Lymphoma (DLBCL), one of the most common, and most studied, types of lymphoma. It is noteworthly that most of what we know about DLBCL arises from studies on lymph nodes, and this is reflected in the present review; however, here we have also included recent information regarding cellular and molecular findings in bone marrow from DLBCL patients. These latter observations may be relevant in opening new lines of research in the near future.

Hematopoiesis↗