Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan: results from a prospective multicenter registry.

The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study.

Quantification of adult T-cell leukemia/lymphoma cells using simple four-color flow cytometry.

Background: The absolute number of adult T-cell leukemia/lymphoma (ATL) cells in peripheral blood is an essential indicator to evaluate disease status. However, microscopically counting ATL cells based on morphology requires experience and tends to be inaccurate due to the rarity of ATL.

Methods: Based on our research showing that acute-type ATL cells are specifically enriched in the CD4+/CD7- (CD7N) fraction, a new analytical method to accurately quantify ATL cells was established using an internal bead standard and simple four-color flow cytometry.

Clinical characteristics and treatment outcome in 65 cases with refractory cytopenia of childhood defined according to the WHO 2008 classification.

This study analysed 65 children who were prospectively registered between 1999 and 2008 and fulfilled the World Health Organization 2008 criteria of refractory cytopenia of childhood (RCC). First-line therapy was determined by the treating physicians: 25 patients received immunosuppressive therapy (IST), 12 patients received haematopoietic stem cell transplantation (HSCT) and one patient received intensive chemotherapy. The remaining 27 patients were followed without treatment for more than 2 years (watch and wait; WW).

Clinical characteristics of 15 children with juvenile myelomonocytic leukaemia who developed blast crisis: MDS Committee of Japanese Society of Paediatric Haematology/Oncology.

Juvenile myelomonocytic leukaemia (JMML) is a rare haematopoietic stem cell disease of early childhood, which can progress to blast crisis in some children. A total of 153 children diagnosed with JMML were reported to the Myelodysplastic Syndrome Committee in Japan between 1989 and 2007; 15 of them (9·8%) had 20% or more blasts in the bone marrow (blast crisis) during the disease course. Blast crisis occurred during observation without therapy (n = 3) or with oral 6-mercaptopurine treatment (n = 9) and in relapse after haematopoietic stem cell transplantation (HSCT; n = 3).

[Prognosis of 75 patients with juvenile myelomonocytic leukemia: prospective study by MDS committee in the Japanese Society of Pediatric Hematology].

Juvenile myelomonocytic leukemia (JMML) is a myelodysplastic/myeloproliferative disorder of young children. Because the disease is rare and the diagnosis is difficult, a prospective registration of patients suspected of having JMML with a pathological central review have been conducted by the MDS Committee of the Japanese Society of Pediatric Hematology. Between 1999 and 2006, 75 children with JMML were enrolled and diagnosed through this system.

Leukemic T cells are specifically enriched in a unique CD3(dim) CD7(low) subpopulation of CD4(+) T cells in acute-type adult T-cell leukemia.

The morphological discrimination of leukemic from non-leukemic T cells is often difficult in adult T-cell leukemia (ATL) as ATL cells show morphological diversity, with the exception of typical "flower cells." Because defects in the expression of CD3 as well as CD7 are common in ATL cells, we applied multi-color flow cytometry to detect a putative leukemia-specific cell population in the peripheral blood from ATL patients. CD4(+) CD14(-) cells subjected to two-color analysis based on a CD3 vs CD7 plot clearly demonstrated the presence of a CD3(dim) CD7(low) subpopulation in each of nine patients with acute-type ATL.

Clinicopathological characteristics of erythroblast-rich RAEB and AML M6a in children.

The distinction between RAEB, RAEB-T and AML M6a is difficult when erythroblasts in the bone marrow (BM) exceed 50%. We analyzed 19 children (2 RAEB, 13 RAEB-T and 4 AML M6a) enrolled in a prospective pathological central review in Japan and divided them into two groups according to the myeloblasts percentage among non-erythroid cells in BM: group A (n = 8), 5-19% myeloblasts; group B (n = 11), 20% or more myeloblasts. Their characteristics were very similar except for the number of myeloblasts.

Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis.

A critical issue for clinical utilization of human ES cells (hESCs) is whether they can generate terminally mature progenies with normal function. We recently developed a method for efficient production of hematopoietic progenitors from hESCs by coculture with murine fetal liver-derived stromal cells. Large numbers of hESCs-derived erythroid progenitors generated by the coculture enabled us to analyze the development of erythropoiesis at a clone level and investigate their function.

Novel method for efficient production of multipotential hematopoietic progenitors from human embryonic stem cells.

We propose a novel method for the efficient production of hematopoietic progenitors from human embryonic stem cells (hESC) via coculture with murine fetal liver-derived stromal cells, in which embryonic hematopoiesis dramatically expands at midgestation. We generated various hematopoietic progenitors in coculture, and this hematopoietic activity was concentrated in cobblestone-like cells derived from differentiated hESC. The cobblestone-like cells mostly expressed CD34 and retained an endothelial cell potential.

RAS-blocking bisphosphonate zoledronic acid inhibits the abnormal proliferation and differentiation of juvenile myelomonocytic leukemia cells in vitro.

Juvenile myelomonocytic leukemia (JMML) is a clonal myeloproliferative/myelodysplastic disorder of early childhood with a poor prognosis. JMML cells are characterized by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) caused by a continuously activated GM-CSF receptor-retrovirus-associated sequence (RAS) signal transduction pathway through various molecular mechanisms, resulting in spontaneous GM colony formation in vitro. Bisphosphonate zoledronic acid (ZOL), a RAS-blocking compound, suppressed colony formation from bone marrow (BM) cells of 8 patients with JMML and 5 healthy control subjects without and with GM-CSF (10 ng/mL), respectively, in a dose-dependent manner in clonal culture.