Mongolian and Japanese Joint Conference on "Echinococcosis: diagnosis, treatment and prevention in Mongolia" June 4, 2009

The first Mongolian-Japanese Joint Conference on "Echinococcosis: diagnosis, treatment and prevention in Mongolia" was held in Ulaanbaatar on June 4th, 2009. It was the first chance for Mongolian experts (clinicians, pathologists, parasitologists, biologists, epidemiologists, veterinarians and others working on echinococcosis) joined together. Increase in the number of cystic echinococcosis (CE) cases year by year was stressed. CE in children may be more than adult cases. Alveolar echinococcosis was suspected chronic malignant hepatic tumors or abscesses. Main discussion was as to how to introduce modern diagnostic tools for pre-surgical diagnosis, how to establish the national system for the data base of echinococcosis with the establishment of a network system by experts from different areas. The importance of molecular identification of the parasites in domestic and wild animals was also stressed

Heterogeneous genetic and non-genetic mechanisms contribute to response and resistance to azacitidine monotherapy

Acute myeloid leukaemia is prevalent in older patients that are often ineligible for intensive chemotherapy and treatment options remain limited with azacitidine being at the forefront. Azacitidine has been used in the clinic for decades, however, we still lack a complete understanding of the mechanisms by which the drug exerts its anti-tumour effect. To gain insight into the mechanism of action, we defined the mutational profile of sequential samples of patients treated with azacitidine. We did not identify any mutations that could predict response and observed lack of a uniform pattern of clonal evolution. Focusing on responders, at remission, we observed three types of response: (1) an almost complete elimination of mutations (33%), (2) no change (17%), and (3) change with no discernible pattern (50%). Heterogeneous patterns were also observed at relapse, with no clonal evolution between remission and relapse in some patients. Lack of clonal evolution suggests that non-genetic mechanisms might be involved. Towards understanding such mechanisms, we investigated the immune microenvironment in a number of patients and we observed lack of a uniform response following therapy. We identified a higher frequency of cytotoxic T cells in responders and higher frequency of naïve helper T cells in non-responders

A novel model of human lympho-myeloid progenitor hierarchy based on single cell functional and transcriptional analysis

Human hemopoiesis produces 10 billion new, terminally mature, blood cells daily; a production that is also rapidly responsive to external change. Dysregulation of this complex process can lead to hemopoietic and immune deficiencies and blood cancers. In humans the hemopoietic progenitor hierarchy producing lymphoid and granulocytic-monocytic (myeloid) lineages is unclear. Multiple progenitor populations give rise to lymphoid and myeloid cells but they remain incompletely characterized at the immunophenotypic, transcriptional and functional level

Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay

The megakaryocyte/erythroid Transient Myeloproliferative Disorder (TMD) in newborns with Down Syndrome (DS) occurs when N-terminal truncating mutations of the hemopoietic transcription factor GATA1, that produce GATA1short protein (GATA1s), are acquired early in development. Prior work has shown that murine GATA1s, by itself, causes a transient yolk sac myeloproliferative disorder. However, it is unclear where in the hemopoietic cellular hierarchy GATA1s exerts its effects to produce this myeloproliferative state. Here, through a detailed examination of hemopoiesis from murine GATA1s ES cells and GATA1s embryos we define defects in erythroid and megakaryocytic differentiation that occur relatively late in hemopoiesis. GATA1s causes an arrest late in erythroid differentiation in vivo, and even more profoundly in ES-cell derived cultures, with a marked reduction of Ter-119 cells and reduced erythroid gene expression. In megakaryopoiesis, GATA1s causes a differentiation delay at a specific stage, with accumulation of immature, kit-expressing CD41hi megakaryocytic cells. In this specific megakaryocytic compartment, there are increased numbers of GATA1s cells in S-phase of cell cycle and reduced number of apoptotic cells compared to GATA1 cells in the same cell compartment. There is also a delay in maturation of these immature GATA1s megakaryocytic lineage cells compared to GATA1 cells at the same stage of differentiation. Finally, even when GATA1s megakaryocytic cells mature, they mature aberrantly with altered megakaryocyte-specific gene expression and activity of the mature megakaryocyte enzyme, acetylcholinesterase. These studies pinpoint the hemopoietic compartment where GATA1s megakaryocyte myeloproliferation occurs, defining where molecular studies should now be focussed to understand the oncogenic action of GATA1s

A novel model of human lympho-myeloid progenitor hierarchy based on single cell functional and transcriptional analysis

Human hemopoiesis produces 10 billion new, terminally mature, blood cells daily; a production that is also rapidly responsive to external change. Dysregulation of this complex process can lead to hemopoietic and immune deficiencies and blood cancers. In humans the hemopoietic progenitor hierarchy producing lymphoid and granulocytic-monocytic (myeloid) lineages is unclear. Multiple progenitor populations give rise to lymphoid and myeloid cells but they remain incompletely characterized at the immunophenotypic, transcriptional and functional level